Surveillance of medication use: early identification of poor adherence

Background: We sought to measure population-level adherence to antihyperlipidemics, antihypertensives, and oral hypoglycemics, and to develop a model for early identification of subjects at high risk of long-term poor adherence. Methods Prescription-filling data for 2 million subjects derived from a payor's insurance claims were used to evaluate adherence to three chronic drugs over 1 year. We relied on patterns of prescription fills, including the length of gaps in medication possession, to measure adherence among subjects and to build models for predicting poor long-term adherence. Results: All prescription fills for a specific drug were sequenced chronologically into drug eras. 61.3% to 66.5% of the prescription patterns contained medication gaps >30 days during the first year of drug use. These interrupted drug eras include long-term discontinuations, where the subject never again filled a prescription for any drug in that category in the dataset, which represent 23.7% to 29.1% of all drug eras. Among the prescription-filling patterns without large medication gaps, 0.8% to 1.3% exhibited long-term poor adherence. Our models identified these subjects as early as 60 days after the first prescription fill, with an area under the curve (AUC) of 0.81. Model performance improved as the predictions were made at later time-points, with AUC values increasing to 0.93 at the 120-day time-point. Conclusions: Dispensed medication histories (widely available in real time) are useful for alerting providers about poorly adherent patients and those who will be non-adherent several months later. Efforts to use these data in point of care and decision support facilitating patient are warranted

Scalable Decision Support at the Point of Care: A Substitutable Electronic Health Record App for Monitoring Medication Adherence

Background: Non-adherence to prescribed medications is a serious health problem in the United States, costing an estimated $100 billion per year. While poor adherence should be addressable with point of care health information technology, integrating new solutions with existing electronic health records (EHR) systems require customization within each organization, which is difficult because of the monolithic software design of most EHR products. Objective: The objective of this study was to create a published algorithm for predicting medication adherence problems easily accessible at the point of care through a Web application that runs on the Substitutable Medical Apps, Reusuable Technologies (SMART) platform. The SMART platform is an emerging framework that enables EHR systems to behave as “iPhone like platforms” by exhibiting an application programming interface for easy addition and deletion of third party apps. The app is presented as a point of care solution to monitoring medication adherence as well as a sufficiently general, modular application that may serve as an example and template for other SMART apps. Methods: The widely used, open source Django framework was used together with the SMART platform to create the interoperable components of this app. Django uses Python as its core programming language. This allows statistical and mathematical modules to be created from a large array of Python numerical libraries and assembled together with the core app to create flexible and sophisticated EHR functionality. Algorithms that predict individual adherence are derived from a retrospective study of dispensed medication claims from a large private insurance plan. Patients’ prescription fill information is accessed through the SMART framework and the embedded algorithms compute adherence information, including predicted adherence one year after the first prescription fill. Open source graphing software is used to display patient medication information and the results of statistical prediction of future adherence on a clinician-facing Web interface. Results: The user interface allows the physician to quickly review all medications in a patient record for potential non-adherence problems. A gap-check and current medication possession ratio (MPR) threshold test are applied to all medications in the record to test for current non-adherence. Predictions of 1-year non-adherence are made for certain drug classes for which external data was available. Information is presented graphically to indicate present non-adherence, or predicted non-adherence at one year, based on early prescription fulfillment patterns. The MPR Monitor app is installed in the SMART reference container as the “MPR Monitor”, where it is publically available for use and testing. MPR is an acronym for Medication Possession Ratio, a commonly used measure of adherence to a prescribed medication regime. This app may be used as an example for creating additional functionality by replacing statistical and display algorithms with new code in a cycle of rapid prototyping and implementation or as a framework for a new SMART app. Conclusions: The MPR Monitor app is a useful pilot project for monitoring medication adherence. It also provides an example that integrates several open source software components, including the Python-based Django Web framework and python-based graphics, to build a SMART app that allows complex decision support methods to be encapsulated to enhance EHR functionality

Sodium Cyclopentadienide as a New Type of Electrolyte for Sodium Batteries

Owing to the low cost and high abundance of sodium, sodium‐based batteries, especially those employing metallic sodium anodes, are considered for post‐lithium energy storage. In order to develop high‐performance and long‐lasting sodium‐metal batteries, however, the reversible Na‐metal stripping and plating challenge must be addressed. Most organic electrolytes suffer from non‐uniform and continuous formation of the solid electrolyte interphase as well as unfavorable dendritic growth. The use of sodium cyclopentadienide dissolved in tetrahydrofuran as the electrolyte reveals an improved reversibility of sodium dissolution and electrodeposition combined with an electrochemical stability window of around 2.2 V vs. Na/Na+ and an ionic conductivity of 1.36 mS cm−1 at 25 °C. Furthermore, the plated electrodes showed a remarkable morphology of the Na deposits, that is, no dendrite formation, whereby the above‐mentioned electrolyte could overcome the aforementioned cycling issues, thus suggesting suitability for further studies

Early Detection of Poor Adherers to Statins: Applying Individualized Surveillance to Pay for Performance

Background: Medication nonadherence costs $300 billion annually in the US. Medicare Advantage plans have a financial incentive to increase medication adherence among members because the Centers for Medicare and Medicaid Services (CMS) now awards substantive bonus payments to such plans, based in part on population adherence to chronic medications. We sought to build an individualized surveillance model that detects early which beneficiaries will fall below the CMS adherence threshold. Methods: This was a retrospective study of over 210,000 beneficiaries initiating statins, in a database of private insurance claims, from 2008-2011. A logistic regression model was constructed to use statin adherence from initiation to day 90 to predict beneficiaries who would not meet the CMS measure of proportion of days covered 0.8 or above, from day 91 to 365. The model controlled for 15 additional characteristics. In a sensitivity analysis, we varied the number of days of adherence data used for prediction. Results: Lower adherence in the first 90 days was the strongest predictor of one-year nonadherence, with an odds ratio of 25.0 (95% confidence interval 23.7-26.5) for poor adherence at one year. The model had an area under the receiver operating characteristic curve of 0.80. Sensitivity analysis revealed that predictions of comparable accuracy could be made only 40 days after statin initiation. When members with 30-day supplies for their first statin fill had predictions made at 40 days, and members with 90-day supplies for their first fill had predictions made at 100 days, poor adherence could be predicted with 86% positive predictive value. Conclusions: To preserve their Medicare Star ratings, plan managers should identify or develop effective programs to improve adherence. An individualized surveillance approach can be used to target members who would most benefit, recognizing the tradeoff between improved model performance over time and the advantage of earlier detection

S100P enhances the motility and invasion of human trophoblast cell lines

S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation

Tunicamycin induced endoplasmatic reticulum changes in endothelial cells investigated in vitro by confocal Raman imaging

This paper describes how tunicamycin (Tu), the most widely used pharmacological agent for inducing endoplasmic reticulum (ER) stress, interacts with endothelial cells. Our results show that tunicamycin enters the cells and accumulates within the ER area. ER stress takes place when improperly folded or damaged proteins begin to accumulate; however, spectroscopic markers of these changes have not been identified as yet. In this work, Raman spectroscopy and scanning electron microscopy imaging of individual endothelial cells treated with Tu were performed. The changes in the biochemical composition of endothelial cells induced by Tu attributed to ER stress were studied in detail. A main feature of the Tu impact on the cells was a decrease of the phospholipid content in the area of ER, and the most abundant lipid with phosphorus groups found there, was identified as sphingomyelin

U-Pb zircon geochronology and geochemical characterization of pre-Alpine metagranitoids and metasediments of the Seckau Nappe System, Eastern Alps

Neue petrographische, geochemische und geochronologische Daten von Paragneisen und Metagranitoiden des Seckau-Komplexes ermöglichen tiefe Einblicke in die voralpidisch gebildete kontinentale Kruste der Ostalpen. Basierend auf diesen neuen Daten kann das kristalline Grundgebirge des Seckau-Komplexes in die nacholgenden drei lithostratigraphischen Einheiten gegliedert werden. (1) Die Glaneck Metamorphic Suite besteht vorwiegend aus feinkörnigen Paragneisen (und Glimmerschiefern) die ein U-Pb-Zirkonalter zwischen 572 7 Ma und 559 11 Ma aufweisen. Diese präkambrischen Paragneisse bilden den kristallinen Rahmen für die nachfolgend eindringenden Plutonite der Hochreichart Plutonic Suite und der Hintertal Plutonic Suite. (2) Die Hochreichart Plutonic Suite besteht hauptsächlich aus leicht bis stark deformierten Graniten und Granodioriten, die einen peraluminösen Charakter (A / CNK = 1,08-1,51), ein Rb/Sr Verhältnis > 45, eine negative Eu-Anomalie sowie U-P Zirkonalter zwischen 508 9 Ma und 486 9 Ma zeigen. Diese spät-kambrischen bis früh-ordovizischen Gesteine sind selten in den Ostalpen zu finden und spiegeln wahrscheinlich die Wiederanbindung des Cadomischen Bogens an Gondwana wider (3) Die Hintertal Plutonic Suite umfasst hauptsächlich leicht bis stark deformierte Intrusivgesteine mit einer intermediären bis sauren Zusammensetzung. Diese Gesteine weisen einen meta- bis peraluminösen Charakter (A /CNK = 0,88 bis 1,23), einen Fraktionierungstrend mit Rb/Sr Verhältnissen 45 sowie U-Pb Zirkonalter im Bereich von 365 11 Ma bis 343 12 Ma auf. Aufgrund petrographischer und geochemischer Merkmale kann die Hintertal Plutonic Suite weiter in den (a) Pletzen Pluton und (b) den Griessstein Pluton unterteilt werden. Der Pletzen Pluton setzt sich aus intermediären bis sauren Intrusivkörpern zusammen, die einen meta- bis leicht peraluminösen (A / CNK = 0,88 bis 1,10) Charakter sowie keine Eu-Anomalie aufweisen. Diese Gesteine zeigen typischerweise große Titanite und Biotite mit einer grünen Eigenfarbe unter dem Lichtmikroskop. Die überwiegend sauren Gesteine des Griessstein Plutons repräsentieren stark fraktionierte Schmelzen, die einen peraluminösen Charakter (A / CNK = 1,10 bis 1,23) und eine nur schwach ausgeprägte Eu-Anomalie zeigen. Die Intrusivgesteine des Pletzen Plutons können mit dem Subduktionsereignis der Paleotethys infolge der Kollision von Gondwana und Laurussia in Verbindung gebracht werden. Die Gesteine des Griessstein Plutons repräsentieren vermutlich fraktionierte Schmelzen der primitiveren Pletzen Schmelze. Neben umfassenden Untersuchungen des Seckau-Komplexes wurde auch dessen sedimentäre Bedeckung, die Rannach Formation, untersucht. Das Altersspektrum der detritären Zirkone der sedimentären Gesteine der Rannach Formation umfasst neoarchäische bis paläoproterozoische (z.B.: 2063 30 Ma), spät-neoproterozoische (555 7 Ma), kambrische (508 7 Ma), ordovizische (457 7 Ma), spät-devonische/früh-karbonische (358 5 Ma) und permische (293 6 Ma) Alter. Diese U-Pb Alter spiegeln dieselben Alter wider, wie sie in den verschiedenen Einheiten des Seckau-Komlexes beobachtet wurden. Einzig ordovizische und permische Zirkonalter wurden in den Gesteinen des Seckau-Komplexes nicht dokumentiert und lassen auf ein regionaleres Liefergebiet schließen.New petrographic, geochemical and geochronological data from paragneisses and metagranitoids of the Seckau Complex allow deeper insights into the pre-Alpine continental crust of the Eastern Alps. Based on these data a new subdivision of the crystalline basement of the Seckau Complex, into the following three lithostratigraphic sub-units, is proposed. (1) The Glaneck Metamorphic Suite is mainly composed of fine-grained paragneisses (and mica schists) that yield U-Pb zircon ages between 572 7 Ma and 559 11 Ma. These pre-Cambrian paragneisses are the host rock for the two subsequent intrusion events represented by plutonic bodies of the Hochreichart Plutonic Suite and the later emplaced Hintertal Plutonic Suite. (2) The Hochreichart Plutonic Suite is mainly composed of less to strong deformed granites and granodiorites indicating a peraluminous character (A/CNK = 1.08-1.51), a Rb/Sr ratio > 45, a significant negative Eu anomaly as well as U-Pb zircon ages in the range from 508 9 Ma to 486 9 Ma. These late Cambrian to Early Ordovician rocks are not very common in the Eastern Alps and reflect most likely the re-attachment event of the Cadomian Arc to Gondwana. (3) The Hintertal Plutonic Suite mainly comprises slightly to strongly deformed intermediate to acidic intrusion bodies. They display a meta- to peraluminous character (A/CNK = 0.88-1.23), a magmatic fractionation trend with Rb/Sr ratios 0.45 and U-Pb zircon ages in the range between 365 11 Ma and 343 12 Ma. Based on petrographic and geochemical characteristics the Hintertal Plutonic Suite can be further subdivided into (a) the Pletzen Pluton and (b) the Griessstein Pluton. The Pletzen Pluton is composed of intermediate to acidic intrusion bodies that are mainly meta- to weakly peraluminous in composition (A/CNK = 0.88 to 1.10) and show no significant Eu anomaly. Large-sized titanite crystals and green-colored biotite minerals, observed under a microscope, characterize this sub-unit. In contrast, the predominantly acidic rocks of the Griessstein Pluton indicate a more fractionated melt with a peraluminous character (A/CNK= 1.10 to 1.23) and a weakly developed Eu anomaly. The intrusive rocks of the Pletzen Pluton can be related to the subduction process of the Paleotethys prior to the collision event of Gondwana and Laurussia. The rocks of the Griessstein Pluton are considered to represent the fractionation product from the more primitive Pletzen melt. In addition to comprehensive investigations of the Seckau Complex its sedimentary cover, the Rannach Formation, was also examined. The detrital zircon age spectrum of sedimentary rocks from the Rannach Formation indicates a wide range of ages including Neoarchean to Paleoproterozoic (e.g., 2063 30 Ma), late Neoproterozoic (555 7 Ma), Cambrian (508 7 Ma), Ordovician (457 7 Ma), Late Devonian/early Carboniferous (358 5 Ma) and Permian (293 6 Ma) ages. These U-Pb zircon ages display predominantly the same ages as observed from different basement units of the Seckau Complex. Only Ordovician and Permian zircon ages are not documented in the rocks of the Seckau Complex and suggest more regional sources.Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Dissertation, 2019(VLID)468056

Increased intestinal permeability in primary Sjögren's syndrome and multiple sclerosis

There is increasing evidence suggesting a role of intestinal dysfunction in a number of autoimmune diseases. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with a documented increased level of intestinal inflammation, whereas multiple sclerosis (MS) is an organ-specific autoimmune disease known to exhibit increased intestinal permeability. In this study we determine to what extent intestinal inflammation, analysed by a faecal calprotectin ELISA, is accompanied by altered intestinal wall permeability, as measured by a lactulose and mannitol intestinal absorption assay. Intestinal permeability was increased in both pSS and MS patients, while faecal calprotectin was elevated in pSS but normal in MS. Our findings suggest different mechanisms mediating a leaky gut in these two diseases: in pSS there is autoimmune attack directly on the intestinal wall; in MS, with autoimmunity being limited to the CNS, it may be due to a disturbed CNS regulation of enteric nerve function

Sodium Cyclopentadienide as a New Type of Electrolyte for Sodium Batteries

Owing to the low cost and high abundance of sodium, sodium‐based batteries, especially those employing metallic sodium anodes, are considered for post‐lithium energy storage. In order to develop high‐performance and long‐lasting sodium‐metal batteries, however, the reversible Na‐metal stripping and plating challenge must be addressed. Most organic electrolytes suffer from non‐uniform and continuous formation of the solid electrolyte interphase as well as unfavorable dendritic growth. The use of sodium cyclopentadienide dissolved in tetrahydrofuran as the electrolyte reveals an improved reversibility of sodium dissolution and electrodeposition combined with an electrochemical stability window of around 2.2 V vs. Na/Na+ and an ionic conductivity of 1.36 mS cm−1 at 25 °C. Furthermore, the plated electrodes showed a remarkable morphology of the Na deposits, that is, no dendrite formation, whereby the above‐mentioned electrolyte could overcome the aforementioned cycling issues, thus suggesting suitability for further studies