Multiple sclerosis in Somali Americans: Nature or nurture?

Background: Differences in the MS course between White and Black populations is well accepted. The existence of a large Somali immigrant population in Minnesota facilitates a study of MS characteristics in this immigrant native African population. The objective of this study was to compare Somali American (SA), African American (AA), and White American (WA) persons with MS (pwMS) regarding clinical features and disease modifying therapy (DMT) use.

Electronic Consultations in a Community Neurology Practice: A Retrospective Study Informing Best Practice.

Objective: To describe our practice of electronic consultations (e-consults) and assess safety and risk factors for subsequent face-to-face consultations.

Patients And Methods: A retrospective cohort study of all e-consults completed in a community neurology practice between May 5, 2018, and June 31, 2019, was completed. Clinical and demographic variables were compared between the successful and unsuccessful (defined by presence of subsequent face-to-face consultation) cohorts.

Impact of Inpatient Initiation of SGLT2 Inhibitors on Diuretic Requirements in Patients With Heart Failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve outcomes in patients with heart failure (HF) and are now included in guideline-directed medical therapy. Trials reporting the change in loop diuretic dose following SGLT2i initiation have indicated conflicting results. There is no clear guidance on whether reducing loop diuretic doses following SGLT2i initiation is appropriate.

Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated randomised, double-blind, placebo-controlled phase 2 study.

Background: A gluten-free diet is insufficient to treat coeliac disease because intestinal injury persists and acute reactions with cytokine release follow gluten exposure. Nexvax2 is a specific immunotherapy using immunodominant peptides recognised by gluten-specific CD4 T cells that might modify gluten-induced disease in coeliac disease. We aimed to assess the effects of Nexvax2 on gluten-induced symptoms and immune activation in patients with coeliac disease.

Blood Pressure Variability Early After Liver Transplantation Predicts Long-Term Mortality.

Cardiovascular disease is a leading cause of mortality after liver transplantation (LT). Elevated blood pressure (BP) in LT recipients (LTRs) is associated with increased cardiovascular events (CVEs) and decreased survival. Increased visit-to-visit BP variability in the general population is associated with adverse outcomes.

A Sensitive Whole Blood Assay Detects Antigen-Stimulated Cytokine Release From CD4+ T Cells and Facilitates Immunomonitoring in a Phase 2 Clinical Trial of Nexvax2 in Coeliac Disease.

Improved blood tests assessing the functional status of rare gluten-specific CD4+ T cells are needed to effectively monitor experimental therapies for coeliac disease (CD). Our aim was to develop a simple, but highly sensitive cytokine release assay (CRA) for gluten-specific CD4+ T cells that did not require patients to undergo a prior gluten challenge, and would be practical in large, multi-centre clinical trials. We developed an enhanced CRA and used it in a phase 2 clinical trial ("RESET CeD") of Nexvax2, a peptide-based immunotherapy for CD.

Deaths from hepatocellular carcinoma are more likely to occur in medical facilities than deaths from other cancers: 2003-2018.

Place of death is a key indicator of quality of end-of-life care, and most people with a terminal diagnosis prefer to die at home. Home has surpassed the hospital as the most common location of all-cause and total cancer-related deaths in the United States. However, trends in place of death due to hepatocellular carcinoma (HCC), which is uniquely comanaged by hepatologists and oncologists, have not been described.

Appropriateness of Antibiotic Prescribing for Acute Sinusitis in Primary Care: A Cross-sectional Study.

The proportion of sinusitis visits that meet antibiotic prescribing criteria is unknown. Of 425 randomly selected sinusitis visits, 50% (214) met antibiotic prescribing criteria. There was no significant difference in antibiotic prescribing at visits that did (205/214 [96%]) and did not (193/211 [92%]; P = .

Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease.

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5 CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled.

Patient factors influencing acute gluten reactions and cytokine release in treated coeliac disease.

Background: Patients with coeliac disease (CD) commonly report a variety of adverse symptoms to gluten, but descriptions of the symptomatic response in the literature may have been confounded by the presence of food components such as fermentable carbohydrates (FODMAPs) causing symptoms of irritable bowel syndrome independent of gluten. In recent unmasked and masked low FODMAP gluten challenge studies in small groups of treated CD patients, nausea and vomiting were shown to be the key symptoms associated with serum interleukin (IL)-2 release. Our objective was to utilise a large and diverse cohort of people with CD undertaking a standardised gluten food challenge to characterise the demographic, genetic and clinical factors influencing the severity and timing of acute gluten reactions and IL-2 production.

Masked bolus gluten challenge low in FODMAPs implicates nausea and vomiting as key symptoms associated with immune activation in treated coeliac disease.

Background: In patients with coeliac disease, FODMAPs in gluten-containing foods, and participant anticipation of a harmful ('nocebo') effect, may contribute to acute symptoms after gluten challenge.

Aim: To establish acute gluten-specific symptoms linked to immune activation in coeliac disease METHODS: We included 36 coeliac disease patients on a gluten-free diet receiving placebo in the RESET CeD trial. Double-blind, bolus vital wheat gluten (~6-g gluten protein) and sham challenges low in FODMAPs were consumed 2 weeks apart.

Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease.

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions.

Elevated serum interleukin-2 after gluten correlates with symptoms and is a potential diagnostic biomarker for coeliac disease.

Background: Coeliac disease patients on a gluten-free diet experience reactions to gluten, but these are not well characterised or understood. Systemic cytokine release was recently linked to reactivation of gluten immunity in coeliac disease.

Aim: To define the nature and time-course of symptoms and interleukin-2 changes specific for coeliac disease patients.

Randomised clinical trial: a placebo-controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease.

Background: Nexvax2 contains three gluten-derived peptides, intended to tolerize coeliac disease patients to gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen-DQ2.5-positive patients, most notably after an initial dose.

Revisiting Perioperative Hair Removal Practices.

The standard of practice for perioperative hair removal is largely based on research that is outdated and underpowered. Although there is evidence to support the practice of clipping instead of shaving, current recommendations are to remove hair only when absolutely necessary. Human hair is bacteria-laden and challenging to disinfect, and clipping can be a safe method of hair removal that does not damage the skin.

Linking Endogenous Factor Xa Activity, a Biologically Relevant Pharmacodynamic Marker, to Edoxaban Plasma Concentrations and Clinical Outcomes in the ENGAGE AF-TIMI 48 Trial.

Background: We previously reported exogenous antifactor Xa (FXa) activity as a pharmacokinetic surrogate marker for edoxaban plasma concentrations. Inhibition of endogenous FXa activity is a more biologically relevant pharmacodynamic measure of edoxaban activity. Here we describe the value of endogenous FXa activity as a pharmacodynamic marker linking edoxaban concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48).

Considering a new domain for antimicrobial stewardship: Topical antibiotics in the open surgical wound.

The global push to combat the problem of antimicrobial resistance has led to the development of antimicrobial stewardship programs (ASPs), which were recently mandated by The Joint Commission and the Centers for Medicare and Medicaid Services. However, the use of topical antibiotics in the open surgical wound is often not monitored by these programs nor is it subject to any evidence-based standardization of care. Survey results indicate that the practice of using topical antibiotics intraoperatively, in both irrigation fluids and powders, is widespread.

Edoxaban drug-drug interactions with ketoconazole, erythromycin, and cyclosporine.

Aims: Edoxaban, a novel factor Xa inhibitor, is a substrate of cytochrome P450 3 A4 (CYP3A4) and the efflux transporter P-glycoprotein (P-gp). Three edoxaban drug-drug interaction studies examined the effects of P-gp inhibitors with varying degrees of CYP3A4 inhibition.

Methods: In each study, healthy subjects received a single oral dose of 60 mg edoxaban with or without an oral dual P-gp/CYP3A4 inhibitor as follows: ketoconazole 400 mg once daily for 7 days, edoxaban on day 4; erythromycin 500 mg four times daily for 8 days, edoxaban on day 7; or single dose of cyclosporine 500 mg with edoxaban.

Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor Xa.

Edoxaban, a once daily non-vitamin K antagonist oral anticoagulant, is a direct, selective, reversible inhibitor of factor Xa (FXa). In healthy subjects, single oral doses of edoxaban result in peak plasma concentrations within 1.0-2.

Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin.

A population pharmacokinetic model was developed to describe plasma concentrations of mirogabalin and lactam metabolite, obtained following a single oral dose of 5 mg mirogabalin to subjects with varying degrees of renal function.A 2-compartment model was used for both mirogabalin and lactam metabolite. Body weight was a significant covariate on volume of distribution of mirogabalin and lactam metabolite, whereas creatinine clearance significantly affected both renal and nonrenal clearance of mirogabalin.

Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain.

Mirogabalin (DS-5565) is an α2δ-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Nonlinear mixed-effects analyses were performed on average daily pain and on the incidence of the adverse events dizziness and somnolence. These models were used to predict the dose of mirogabalin equivalent to pregabalin and the probability of meaningful reduction in pain compared with placebo and pregabalin.

Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus.

Colesevelam improves glycemic control in patients with type 2 diabetes when added to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter, double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes who had suboptimal glycemic control [HbA1c ≥ 58 mmol/mol (7.

Safety and efficacy of colesevelam HCl in the treatment of elderly patients.

Background And Objectives: Colesevelam significantly lowers cholesterol in patients with hypercholesterolemia, and both cholesterol and hemoglobin A1C (A1C) in patients with type 2 diabetes mellitus (T2DM). The purpose of this post hoc analysis was to evaluate the efficacy and safety/tolerability of colesevelam in older (≥65 years) and younger (<65 years) adults.

Methods: We conducted post hoc analyses of pooled clinical trial data from seven phase II and III randomized, double-blind, placebo-controlled, primary hyperlipidemia and T2DM clinical trials.