A Multi-Intervention Campaign Lowers Pediatric and Young Adult Diabetic Ketoacidosis Hospitalizations in a Canadian Province.

Objectives: The Newfoundland and Labrador diabetic ketoacidosis Project (NLdkaP) is a multi-intervention, province-wide project aimed at lowering rates of diabetic ketoacidosis (DKA) within the pediatric and young adult populations.

Methods: The NLdkaP interventions were first selected, developed and implemented. We then conducted a retrospective study of hospitalization data over three 2-year periods: pre-, during and post-NLdkaP.

Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis.

Background & Aims: Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis.

A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, and lobular inflammation which may lead to fibrosis. Lipotoxicity activates caspases, which cause apoptosis and inflammatory cytokine (IL-1β and IL-18) production. Emricasan is a pan-caspase inhibitor that decreases serum aminotransferases and caspase activation in patients with NASH.

Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension.

Background & Aims: Emricasan, an oral pan-caspase inhibitor, decreased portal pressure in experimental cirrhosis and in an open-label study in patients with cirrhosis and severe portal hypertension, defined as a hepatic venous pressure gradient (HVPG) ≥12 mmHg. We aimed to confirm these results in a placebo-controlled study in patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis.

Methods: We performed a multicenter double-blinded study, randomizing 263 patients with NASH-related cirrhosis and baseline HVPG ≥12 mmHg to twice daily oral emricasan 5 mg, 25 mg, 50 mg or placebo in a 1:1:1:1 ratio for up to 48 weeks.

Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease.

Background: Lipotoxicity leading to excessive caspase-mediated apoptosis and inflammation is believed to drive liver damage in NAFLD. Emricasan is a pan-caspase inhibitor that decreased serum ALT and apoptotic and inflammatory markers in subjects with chronic hepatitis.

Aims: To assess whether 28 days of emricasan would reduce elevated levels of serum ALT, AST, cleaved cytokeratin-18, full-length cytokeratin-18, and caspase 3/7 in subjects with NAFLD and raised aminotransferases.

A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis.

Background: Cirrhosis and acute-on-chronic liver failure (ACLF) are associated with systemic inflammation, and caspase-mediated hepatocyte cell death. Emricasan is a novel, pan-caspase inhibitor. Aims of this study were to assess the pharmacokinetics, pharmacodynamics, safety and clinical outcomes of emricasan in acute decompensation (AD) of cirrhosis.

Role of Social Factors in Glycemic Control Among African American Children and Adolescents with Type 1 Diabetes.

Objective: With the rising incidence of Type 1 diabetes (T1DM), it is important to recognize deficiencies in care and areas of improvement to provide better access to resources and education for T1DM patients. The objective of this study was to recognize social factors and compliance barriers affecting glycated hemoglobin (A1c) level in T1D patients among the minority population.

Methods: A total of 84 T1DM patients, ages 3 to 21 years, 49% males, 87% African American participated in the study.

Emricasan (IDN-6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension.

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis.

Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo.

Background & Aims: Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH).

Methods: We performed a multicenter study of 86 patients with cirrhosis (Child-Pugh class A or B; mean score, 6.

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

Background: Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively.

Reducing episodes of diabetic ketoacidosis within a youth population: a focus group study with patients and families.

Background: Diabetic ketoacidosis (DKA) is the most common cause of morbidity and mortality for youth with type 1 diabetes mellitus (T1DM). This article reports qualitative data from focus groups with youth and parents of youth with T1DM on the barriers that they identify to DKA prevention and resources that may aid youth better manage their diabetes.

Methods: Four focus groups were held in three communities, two rural and one urban, in the Canadian province of Newfoundland and Labrador (NL) with adolescents and parents of youth with diabetes.

Detection of Neorickettsia risticii from various freshwater snail species collected from a district irrigation canal in Nevada County, California.

This study investigated the role of a district irrigation canal in Nevada County, California, USA, as the point source of infection for Neorickettsia risticii, causative agent of equine neorickettsiosis (EN). A total of 568 freshwater snails comprising Juga spp., Planorbella subcrenata (Carpenter, 1857) (Rough Rams-horn), Physella virgata (Gould, 1855) (Protean Physa) and feces from three horses with EN were collected and tested for N.

Interaction of oral bacteria with gingival epithelial cell multilayers.

Primary gingival epithelial cells were cultured in multilayers as a model for the study of interactions with oral bacteria associated with health and periodontal disease. Multilayers maintained at an air-liquid interface in low-calcium medium displayed differentiation and cytokeratin properties characteristic of junctional epithelium. Multilayers were infected with fluorescently labeled Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum or Streptococcus gordonii, and bacterial association was determined by confocal microscopy and quantitative image analysis.

Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate.

Background: Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors.

Objective: To assess structural damage progression through 2 years.

Methods: Intention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months.

Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is elevated in young, complication-free patients with Type 1 diabetes.

Objectives: Elevated advanced glycation endproducts (AGEs) are implicated in diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of the most abundant AGEs in vivo. Our objective was to develop a time-saving, specific method to measure free MG-H in plasma and determine its levels in complication-free young individuals with Type 1 diabetes (T1DM).

The oblique view: an alternative approach for ultrasound-guided central line placement.

Background: Numerous studies have shown significant benefits of using real-time ultrasonography for central line intravenous access. Traditionally, the ultrasound probe is placed along the short axis of the vein to visualize and direct needle placement. This view has some limitations, particularly being able to visualize the needle tip.

Study of glucose profiles with continuous glucose monitoring in adolescents with poorly controlled type 2 diabetes mellitus.

Aim: To evaluate glycemic excursions in adolescents with poorly controlled type 2 diabetes mellitus (DM2).

Methods: Seventeen adolescents (12 F/5 M) underwent glucose monitoring for 3 days using a continuous glucose monitoring system (CGMS). Glucose measurements were divided into periods of euglycemia, hyperglycemia, and hypoglycemia.

Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies.

Objective: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors.

Methods: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation.

Very high and increasing incidence of type 1 diabetes mellitus in Newfoundland and Labrador, Canada.

Objective: To determine the incidence of type 1 diabetes mellitus (T1DM) among children aged 0-14 yr inclusive in the Canadian province of Newfoundland and Labrador (NL).

Methods: Prospective and retrospective cohort study of the incidence of T1DM in children aged 0-14 yr from 1987 to 2005. Identified cases during this time period were ascertained from several sources and verified using the capture-recapture technique.

Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with Type 1 diabetes.

The reactive aldehydes methylglyoxal and glyoxal, arise from enzymatic and non-enzymatic degradation of glucose, lipid and protein catabolism, and lipid peroxidation. In Type 1 diabetes mellitus (T1DM) where hyperglycemia, oxidative stress, and lipid peroxidation are common, these aldehydes may be elevated. These aldehydes form advanced glycation end products (AGEs) with proteins that are implicated in diabetic complications.

Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition.

Background: A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy.

Methods: Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug.

Costimulation blockade with belatacept in renal transplantation.

Background: Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes.