Celiac Disease: Current and Investigational Therapies and the Role of the Pharmacist

Celiac disease is a genetically-linked autoimmune disease which affects the gastrointestinal tract. It is an inflammatory reaction to ingested gluten-containing substances that produces the most frequent symptoms of abdominal pain, bloating and intermittent or chronic diarrhea. Diagnosis can be made by blood testing for specific IgA autoantibodies and a confirmation duodenal biopsy to look for the characteristic scalloping and villous atrophy that occurs in response to the inflammation. A gluten-free diet, until recently, was the only treatment available and continues to be the mainstay of treatment. Newer adjunct therapies to dietary management include larazotide acetate, peptidases, the use of parasite Necator americanus, a desensitizing vaccine, polymeric binders, cytokine antagonists, tissue transglutaminase inhibitors, probiotics and anti-inflammatory therapy. This review will outline the potential of each of these therapies and discuss the role of the pharmacist in assisting patients with Celiac disease

Computationally Efficient Confidence Intervals for Cross-validated Area Under the ROC Curve Estimates

In binary classification problems, the area under the ROC curve (AUC), is an effective means of measuring the performance of your model. Most often, cross-validation is also used, in order to assess how the results will generalize to an independent data set. In order to evaluate the quality of an estimate for cross-validated AUC, we must obtain an estimate for its variance. For massive data sets, the process of generating a single performance estimate can be computationally expensive. Additionally, when using a complex prediction method, calculating the cross-validated AUC on even a relatively small data set can still require a large amount of computation time. Thus, when the processes of obtaining a single estimate for cross-validated AUC is significant, the bootstrap, as a means of variance estimation, can be computationally intractable. As an alternative to the bootstrap, we demonstrate a computationally efficient influence curve based approach to obtaining a variance estimate for cross-validated AUC

Computational Studies of Intramolecular Hydrogen Atom Transfers in the ß-Hydroxyethylperoxy and ß -Hydroxyethoxy Radicals

The ß-hydroxyethylperoxy (I) and ß-hydroxyethoxy (III) radicals are prototypes of species that can undergo hydrogen atom transfer across their intramolecular hydrogen bonds. These reactions may play an important role in both the atmosphere and in combustion systems. We have used density functional theory and composite electronic structure methods to predict the energetics of these reactions, RRKM/master equation simulations to model the kinetics of chemically activated I, and variational transition state theory (TST) to predict thermal rate constants for the 1,5-hydrogen shift in I (Reaction 1) and the 1,4-hydrogen shift in III (Reaction 2). Our multi-coefficient Gaussian-3 calculations predict that Reaction 1 has a barrier of 23.59 kcal/mol, and that Reaction 2 has a barrier of 22.71 kcal/mol. These predictions agree rather well with the MPW1K and BB1K density functional theory predictions but disagree with predictions based on B3LYP energies or geometries. Our RRKM/master equation simulations suggest that almost 50% of I undergoes a prompt hydrogen shift reaction at pressures up to 10 Torr, but the extent to which I is chemically activated is uncertain. For Reaction 1 at 298 K, the variational TST rate constant is ~30% lower than the conventional TST result, and the microcanonical optimized multidimensional tunneling (OMT) method predicts that tunneling accelerates the reaction by a factor of 3. TST calculations on Reaction 2 reveal no variational effect and a 298 K OMT transmission coefficient of 105. The Eckart method overestimates transmission coefficients for both reactions. [ACS abstract]http://pubs.acs.org/cgi-bin/abstract.cgi/jpcafh/asap/abs/jp0704113.htm

Comparison of Long-Term Oral Anticoagulation Therapies Including Newly Approved Reversal Agent for Dabigatran

Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care professional in order to test their international normalized ratio (INR). Newer anticoagulants, including dabigatran, rivaroxaban and apixaban, do not require frequent INR testing and have a quicker onset of action than warfarin, providing convenience for the patient. However, many health care professionals prefer warfarin because the INR may indicate its efficacy, its dosages can be easily changed and it is typically more affordable. Additionally, dabigatran may be chosen because it is the only one of these drugs that has a reversal agent, which can be utilized in the case of major bleeding or emergent surgery. There are many opportunities for pharmacists to impact patient outcomes in the anticoagulation therapy setting. From clinics to the community pharmacy setting, the pharmacist\u27s role in patient counseling and education is crucial in reducing mortality. Additionally, drug development is a growing market as reversal agents are needed for many of these newer anticoagulation therapies

Triple Therapy or Triple Threat: An Analysis of Triple Antiplatelet Therapy Compared to Dual Antiplatelet Therapy

Triple antiplatelet therapy (TAPT, or triple therapy), is an oral medication regimen designed to reduce the risk of major cardiovascular events. It consists of aspirin, clopidogrel or an alternative, and an oral anticoagulant (OAC). It differs from dual antiplatelet therapy (DAPT) due to inclusion of an OAC. Multiple clinical studies have indicated that triple therapy is more effective at clot prevention, when compared to aspirin monotherapy and DAPT, but is associated with a higher risk of major bleeding. Pharmacists have a key role in determining candidates for DAPT and TAPT regimens. Other opportunities for pharmacists include patient monitoring, counseling and medication review throughout treatment with antithrombotic therapy

Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.

One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse

Pulmonary Rehabilitation in Patients with Respiratory Disease

Background. Limited evidence suggests that pulmonary rehabilitation be included in the management of restrictive lung diseases. The purpose of this study was to document pulmonary rehabilitation outcomes in patients with respiratory diseases other than chronic obstructive pulmonary disease (COPD). Methods. Clinical outcomes of 31patients with respiratory diseases other than COPD and 190 patients with COPD, seen over a 35-month period, were reviewed retrospectively. Patients were evaluated for a 6-minute walk, arm curl strength, chair stand strength, the St. George’s Respiratory Questionnaire (SGRQ) total score, SGRQ symptom scores, SGRQ activity levels, and SGRQ impact of respiratory illness on the patient’s life. Outcome measures were obtained before the start of pulmonary rehabilitation and after a minimum of nine therapy visits. Results. Pre- and post-rehabilitation changes in the 6-minute walk, arm curl strength, chair stand strength, the St. George’s Respiratory Questionnaire (SGRQ) total score, SGRQ symptom scores, SGRQ activity levels, and SGRQ impact scores improved significantly for both groups. However, non-COPD patients achieved significantly higher mean SGRQ impact scores and arm curl strength than patients with COPD. Conclusions. Pulmonary rehabilitation should be recommended for all patients with respiratory disease, not only those with COPD

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112th Congress

This report provides committee funding requests and authorizations as adopted pursuant to primary expense authorizations for House committees in the 104th-112th Congresses