Incidence of Post-ERCP Pancreatitis in Patients Receiving Rectal Indomethacin vs. Compounded Rectal Diclofenac Prophylaxis.

Background And Aims: Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States.

Resolving the H I in damped Lyman α systems that power star formation.

Reservoirs of dense atomic gas (primarily hydrogen) contain approximately 90 per cent of the neutral gas at a redshift of 3, and contribute to between 2 and 3 per cent of the total baryons in the Universe. These 'damped Lyman α systems'-so called because they absorb Lyman α photons within and from background sources-have been studied for decades, but only through absorption lines present in the spectra of background quasars and γ-ray bursts. Such pencil beams do not constrain the physical extent of the systems.

Applying diagnosis support systems in electronic health records to identify wild-type transthyretin amyloid cardiomyopathy risk.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is frequently misdiagnosed, and delayed diagnosis is associated with substantial morbidity and mortality. At three large academic medical centers, combinations of phenotypic features were implemented in electronic health record (EHR) systems to identify patients with heart failure at risk for ATTRwt-CM. Phenotypes/phenotype combinations were selected based on strength of correlation with ATTRwt-CM versus non-amyloid heart failure; different clinical decision support and reporting approaches and data sources were evaluated on Cerner and Epic EHR platforms.

A Network Theory Approach to Curriculum Design.

In this paper we hypothesize that education, especially at the scale of curriculum, should be treated as a complex system composed of different ideas and concepts which are inherently connected. Therefore, the task of a good teacher lies in elucidating these connections and helping students make their own connections. Such a pedagogy allows students to personalize learning and strive to be 'creative' and make meaning out of old ideas.

Safety and Efficacy of Oral Anticoagulants for Atrial Fibrillation in Patients After Bariatric Surgery.

Anticoagulation management is challenging in bariatric surgery patients, due to altered gastrointestinal anatomy and potentially reduced absorption. Few studies have evaluated clinical outcomes in this population. The objective of this study was to compare the efficacy and safety of oral anticoagulants in patients with and without a history of bariatric surgery.

Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma.

There are currently no effective chemotherapeutic drugs approved for the treatment of diffuse intrinsic pontine glioma (DIPG), an aggressive pediatric cancer resident in the pons region of the brainstem. Radiation therapy is beneficial but not curative, with the condition being uniformly fatal. Analysis of the genomic landscape surrounding DIPG has revealed that activin receptor-like kinase-2 (ALK2) constitutes a potential target for therapeutic intervention given its dysregulation in the disease.

Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.

Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant.

Does adherence to child care nutrition and physical activity best practices differ by child care provider's participation in support programs and training?

Introduction: To date, gaps exist in our understanding of how child care provider participation in various support programs is associated with the reported implementation of nutrition and physical activity best practices by child care providers. Thus, the purpose of the current study was to compare implementation of nutrition and physical activity best practices among child care providers engaged in the Child and Adult Food Care Program (CACFP), Parent AWARE, and other training opportunities, to implementation among providers who do not participate in each of these opportunities.

Methods: Cross-sectional analysis of survey data collected from a stratified-random sample of licensed family-home and center-based child care settings (Family-homes n=394; Centers n= 224) in XXX from Month-Month 20XX.

Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m), obese (30-39.9 kg/m), and morbidly obese (⩾ 40 kg/m).

Using knowledge translation for quality improvement: an interprofessional education intervention to improve thromboprophylaxis among medical inpatients.

Background: Low-molecular-weight heparin (LMWH) is an effective means of preventing venous thromboembolism (VTE) among medical inpatients. Compared with unfractionated heparin, LMWH is equivalent or superior in efficacy and risk of bleeding. Despite its advantages, LMWH is underused in VTE prophylaxis for general-medicine patients hospitalized at our institution.

Improving inpatient warfarin therapy safety using a pharmacist-managed protocol.

Introduction: Safe management of warfarin in the inpatient setting can be challenging. At the Mayo Clinic hospitals in Rochester, Minnesota, we set out to improve the safety of warfarin management among surgical and non-surgical inpatients.

Methods: A multidisciplinary team designed a pharmacist-managed warfarin protocol (PMWP) which designated warfarin dosing to inpatient pharmacists with guidance from computerised dosing algorithms.

Performance comparison of two Olympus InnovX handheld x-ray analyzers for feasibility of measuring arsenic in skin in vivo - Alpha and Delta models.

The Figure-Of-Merit (FOM) performance, a combination of detection limit and dose, is compared between two generations of handheld X-Ray Fluorescence (XRF) spectrometers for the feasibility of in vivo XRF measurement of arsenic (As) in skin. The Olympus InnovX Delta model analyzer (40 kVp using either 37 or 17μA) was found to show improvements in Minimum Detection Limit (MDL) using arsenic As-doped skin calibration phantoms with bulk tissue backing, when compared to the first generation InnovX Alpha model (40kVp, 20μA) in 120s measurements. Differences between two different definitions of MDL are discussed.

Going Beyond Administrative Data: Retrospective Evaluation of an Algorithm Using the Electronic Health Record to Help Identify Bleeding Events Among Hospitalized Medical Patients on Warfarin.

To reliably assess quality, a standardized electronic approach is needed to identify bleeding events. The study aims were the following: (1) clinically validate an electronic health record-based algorithm for bleeding and (2) assess interrater results to determine validity and reliability. Data were analyzed before and after implementation of a pharmacist-managed warfarin protocol.

Obesity Prevention in Early Child Care Settings.

Background: Long-term evaluation studies reveal that high-quality early care and education (ECE) programs that include a lifestyle component predict later adult health outcomes. The purpose of this article is to characterize the nutrition and physical activity (PA) practices, including implementation difficulty and barriers, of licensed center- and family home-based ECE programs serving 2- to 5-year-old children in Minnesota (MN) and Wisconsin (WI).

Method: A stratified random sampling procedure was used to select representative cross sections of licensed ECE providers in MN and WI.

Evaluation of cephalexin failure rates in morbidly obese patients with cellulitis.

What Is Known And Objective: Identification of adequate antimicrobial dosing regimens for morbidly obese patients is essential given the simultaneous increase in morbid obesity and cellulitis prevalence in recent years. Insufficient data currently exist to describe the effectiveness of extrapolating traditional antibiotic dosing strategies to morbidly obese patients with cellulitis. The primary objective of this study was to compare therapeutic failure rates in non-obese and morbidly obese patients with cellulitis when treated with cephalexin at standard dosing.

Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods.

In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity.

Mealtime Insulin Dosing by Carbohydrate Counting in Hospitalized Cardiology Patients: A Retrospective Cohort Study.

Background: Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting.

Materials And Methods: This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010-November 7, 2013.

Assessment of the presence and quality of osteoporosis prevention education among at-risk internal medicine patients.

Objective: Appropriate calcium and vitamin D intake for the prevention of osteoporosis represents an important component of osteoporosis prevention education (OPE). We sought to assess the presence and quality of OPE among osteoporotic and at-risk inpatients.

Design: Prospective chart review plus cross-sectional interview.

N- versus O-alkylation: utilizing NMR methods to establish reliable primary structure determinations for drug discovery.

A classic synthetic issue that remains unresolved is the reaction that involves the control of N- versus O-alkylation of ambident anions. This common chemical transformation is important for medicinal chemists, who require predictable and reliable protocols for the rapid synthesis of inhibitors. The uncertainty of whether the product(s) are N- and/or O-alkylated is common and can be costly if undetermined.

Peptide backbone replacement of hepatitis C virus NS3 serine protease C-terminal cleavage product analogs: discovery of potent succinamide inhibitors.

A number of potent peptidic inhibitors of the NS3 protease have been described in the literature based on a substrate-based approach. In an on-going effort to reduce the peptidic character of this class of inhibitors, two novel series of analogs have been prepared in which the usual P3 amino acid residue is replaced by a succinamide fragment. This new backbone modification not only reduces the peptidic nature of traditional inhibitors but also provides new SAR opportunities for the capping group.

Synthesis and optimization of a novel series of HCV NS3 protease inhibitors: 4-arylproline analogs.

In this report we describe the synthesis and evaluation of diverse 4-arylproline analogs as HCV NS3 protease inhibitors. Introduction of this novel P2 moiety opened up new SAR and, in combination with a synthetic approach providing a versatile handle, allowed for efficient exploitation of this novel series of NS3 protease inhibitors. Multiple structural modifications of the aryl group at the 4-proline, guided by structural analysis, led to the identification of analogs which were very potent in both enzymatic and cell based assays.

Compound aggregation in drug discovery: implementing a practical NMR assay for medicinal chemists.

The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that can be performed on equipment prevalent in most synthetic chemistry departments. We show that (1)H NMR resonances are sensitive to large molecular-size entities and to smaller multimers and mixtures of species.