Safety and Effectiveness of an Anti-Xa-based Unfractionated Heparin Protocol for Impella Percutaneous Ventricular Assist Devices.

Background: Impella devices are used for mechanical circulatory support in patients with cardiogenic shock or those undergoing high-risk percutaneous coronary intervention (PCI). Anticoagulation protocols in this population are not well established and are complicated by concomitant use of purge solutions containing unfractionated heparin (UFH) and intravenous UFH continuous infusion (CI) for systemic anticoagulation. Objectives: To evaluate thrombotic and bleeding complications when using a novel UFH protocol with a reduced initial UFH CI dose of 6 units/kg/hour targeting an anti-Xa goal of 0.3 to 0.5 units/mL in patients receiving Impella support. Methods: This single-center, retrospective study included 41 patients on Impella support who received an UFH purge solution and/or an IV UFH infusion. The primary outcome was overall composite bleeding. Secondary outcomes included thrombotic events and systemic UFH exposure. An exploratory analysis was performed to identify risk factors for bleeding. Results: Anti-Xa values were in therapeutic range 46% of the time while on support (interquartile range 16.6%-75%), with a median IV UFH dose of 6 units/kg/hour. The overall bleeding rate was 29.2%, with 6 minor bleeds and 2 major bleeds with no fatal bleeding or intracranial hemorrhage. Rate of overall thrombosis was 4.9%, including 1 ischemic stroke and 1 occurrence of limb ischemia. Conclusion: Use of a modified UFH protocol to target an anti-Xa goal of 0.3 to 0.5 units/mL resulted in bleeding and thrombotic event rates similar to previous literature. This protocol utilizing an initial rate of 6 units/kg/hour may be a useful approach to achieve therapeutic anticoagulation while accounting for UFH exposure from the purge solution and minimizing need for frequent calculations.

Gut microbiome differences among Mexican Americans with and without type 2 diabetes mellitus.

PURPOSE: Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. METHODS: This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. RESULTS: Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. CONCLUSIONS: Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.

National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015.

OBJECTIVE: Despite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years. RESEARCH DESIGN AND METHODS: This cross-sectional study utilized data from the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%. RESULTS: A total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55-73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%). CONCLUSIONS: National ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing.

A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015.

PURPOSE: Gastric acid suppressants are commonly used in the United States, and while generally well-tolerated, long-term use has been associated with infection, bone fractures, and nutrient malabsorption. The purpose of this study was to describe national trends in gastric acid suppressant use over a 7-year period. METHODS: This was a cross-sectional study using data from the National Ambulatory Medical Care Survey from 2009 to 2015. Gastric acid suppressant use was defined as any outpatient visit with a documented prescription for a proton pump inhibitor or histamine-2 receptor antagonist documented during the outpatient visit. Sample data weights were used to extrapolate to national estimates. Use was calculated as the number of prescriptions per total outpatient visits per year. Appropriateness of prescribing was assessed using FDA-approved indications listed in each visit. RESULTS: These data represent 6.8 billion patient outpatient visits between 2009 and 2015, of which nearly 600 million (8.8%) had documented gastric acid suppressant use. The median (IQR) age of gastric acid suppressant users and non-gastric acid suppressant users was 62 (50-73) and 49 (25-65), respectively. Gastric acid suppressant use decreased from 9.0% in 2009 to 7.7% in 2012, and then increased to 9.7% in 2015. Proton pump inhibitor use was slightly higher in the Midwest (8.3%). Only 15.8% of gastric acid suppressant users had a documented indication. CONCLUSIONS: Proton pump inhibitor use increased after 2012, and the majority of gastric acid suppressant users did not have a documented indication. Judicious gastric acid suppressant prescribing needs to be exercised, especially in the context of new safety data regarding long-term proton pump inhibitor use.

Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis.

Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated. Animal studies were excluded. Randomized, controlled trials (RCTs) were prioritized. Results: Four RCTs were identified. In each, pimavanserin was well-tolerated with few adverse effects and no worsening of motor symptoms. A Phase II trial displayed a nonsignificant trend toward Scale for Assessment of Positive Symptoms (SAPS) improvement (p=0.09), with significant benefits in secondary efficacy markers. However, two Phase III trials, including one that was terminated early, failed to show significant SAPS improvement. A third Phase III trial with an improved research design utilized a nine-item subset of the SAPS, the SAPS-PD, as the primary outcome and demonstrated that pimavanserin 40mg was effective in improving PDP compared to placebo (p=0.0014, effect size=0.50). Secondary outcomes were also significantly improved: Clinical Global Impression of Severity (CGI-S) (p=0.0007, effect size=0.52) and Clinical Global Impression of Improvement (CGI-I) (p=0.0011, effect size=0.51), caregiver burden (p=0.0016, effect size=0.50), nighttime sleep (p=0.0446, effect size=0.31), and daytime wakefulness (p=0.012, effect size=0.39). Conclusion: Evidence suggests pimavanserin attenuates PDP symptoms with few adverse effects and little risk of worsening motor function. With limited treatment options for PDP, pimavanserin represents an important therapeutic innovation.