Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial

Glucose measurement in intensive care medicine is performed intermittently with the risk of undetected hypoglycemia. The workload for the ICU nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM) systems are available and may be able to solve some of these issues in critically ill patients. In a randomized controlled design in a mixed ICU in a teaching hospital we compared the use of subcutaneous CGM with frequent point of care (POC) to guide insulin treatment. Adult critically ill patients with an expected stay of more than 24 hours and in need of insulin therapy were included. All patients received subcutaneous CGM. CGM data were blinded in the control group, whereas in the intervention group these data were used to feed a computerized glucose regulation algorithm. The same algorithm was used in the control group fed by intermittent POC glucose measurements. Safety was assessed with the incidence of severe hypoglycemia ( <2.2 mmol/L), efficacy with the percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed nursing workload and costs. In this study, 87 patients were randomized to the intervention and 90 to the control group. CGM device failure resulted in 78 and 78 patients for analysis. The incidence of severe glycemia and percentage of time within target range was similar in both groups. A significant reduction in daily nursing workload for glucose control was found in the intervention group (17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly reduced with EUR 12 (95% CI -32 to -18, P = 0.02) in the intervention group. Subcutaneous CGM to guide insulin treatment in critically ill patients is as safe and effective as intermittent point-of-care measurements and reduces nursing workload and daily costs. A new algorithm designed for frequent measurements may lead to improved performance and should precede clinical implementation. Clinicaltrials.gov, NCT01526044. Registered 1 February 201

Safety and Cost-effectiveness Analysis of DPYD*2A pharmacogenetic guided dosing in patients treated with Capecitabine or 5-FU

Background Fluoropyrimidines are a rationally developed class of anticancer agents that are widely prescribed in clinical use of cancer patients. Adverse events of fluoropyrimidines are prominent. This can be explained by the initial and rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD) what catabolizes 5-FU. Patients with partial deficiency of this enzyme are at risk of developing severe 5-FU associated toxicity. The polymorphism DPYD*2A in the DPYD gene is most described as cause of decreased DPD activity with serious clinical relevance. Frequency of DPYD*2A is estimated between 1.0-2.0%. No routinely screening for DPD deficiency is performed yet prior to start of fluoropyrimidine treatment. The main aim of this study was to show that fluoropyrimidine-induced toxicity can significantly be reduced by dose adaption prior to start of therapy in DPYD*2A mutant patients and to demonstrate that this screening strategy is cost-saving. Methods Screening for DPYD*2A was performed in 854 Dutch cancer patients who were considered for treatment with Capecitabine or 5-FU. DPYD*2A mutants received adaptive dose with at least 50 % reduction. DPYD*2A wild type patients received conventionally dose. Patient files were investigated on general patient- and treatment characteristics, the toxicity profile and hospitalization and noted in an electronic CRF. Toxicity outcome in the prospective determined DPYD*2A mutant patients was compared to retrospectively determined DPYD*2A mutants. The cost-effectiveness analysis was carried out by using a decision tree and a multiple-state decision analytical model. Results Frequency of the DPYD*2A polymorphism in this prospective Dutch cancer population was 1.5 %. Of the 13 found DPYD*2A heterozygous mutants, 7 patients received treatment in adaptive dose. There was a beneficial toxicity profile without hospitalization due to adaptive dosing in these DPYD*2A mutant patients. Comparison of toxicity outcome in prospective vs. retrospective determined DPYD*2A mutant patients showed a significant difference in toxicity (diarrhea, P = 0.012; hematological P = 0.004; mucositis P = 0.016; any grade ot toxicity P < 0.001). Cost-effectiveness analysis showed favorable economic perspective in expected costs for the screening strategy vs. usual care (non screening): €5,750.13 vs. €5,829.39. Saved costs are €79.26 per patient with 1 percent reduction in severe toxicity. Considering the yearly amount of fluoropyrimidine treatments the save-costing will be at least €554,820. Discussion & Conclusions The present study shows that screening for the DPYD*2A mutation prior to start of fluoropyrimidine therapy provides significant reduction in fluoropyrimidine-associated toxicity and hospitalization in DPYD*2A mutant patients treated in adaptive dose. In addition, the favorable economic perspective for screening in our cost-effectiveness analysis suggests that screening should become standard of care in the treatment with fluoropyrimidines. However, pharmacogenetic screening is just one approach, screening for just one coding mutation alone cannot identify all patients at risk.

Die praktische Umsetzung der Leistungs- und Entgeltverordnung 2015 in den heilpädagogischen Institutionen : mit dem Hauptaugenmerk auf die Bereiche des Erwachsenenwohnens und der Teilhabe an Beschäftigung in der Arbeitswelt (TaB)

Die vorliegende Arbeit beschäftigt sich mit der Umsetzung der Leistungs- und Entgeltverordnung 2015 in den heilpädagogischen Einrichtungen. Im Speziellen beschäftigt sich diese Arbeit mit den zwei Bereichen Erwachsenenwohnen und Teilhabe an Beschäftigung in der Arbeitswelt, kurz TaB. Dafür gibt diese Arbeit einen Überblick über das österreichweite und steiermärkische Behindertengesetz, welche sich sehr ähneln aber in den Details unterscheiden, über die Definition von Behinderung allgemein und von geistiger Behinderung und den Aufbau der Leistungs- und Entgeltverordnung und ihre zwei Bereiche Erwachsenenwohnen und Teilhabe an Beschäftigung in der Arbeitswelt. Des Weiteren wird die Weltgesundheitsorganisation und ihr Klassifizierungssystem, welche versucht mit ihrer Einteilung und Beschreibung eine allgemein gültige Definition von Behinderung zu entwickeln, und den Nationalen Aktionsplan Behinderung beschrieben. Ebenfalls wird die UN-Behindertenrechtskonvention, welche Österreich unterschrieben und ratifiziert hat, beschrieben. Doch die Arbeit mit Menschen mit Behinderungen besteht nicht nur aus Verordnungen, Gesetze oder Konventionen, sondern sie besteht auch aus den methodischen Grundlagen, wie zum Beispiel dem Normalisierungsprinzip, dem Empowerment-Konzept, der Selbstbestimmung, der Partizipation und der SIVUS-Methode. Das Hauptaugenmerk liegt, wie bereits erwähnt, auf der praktischen Umsetzung der Verordnung, sowie die Vorteile und Problemstellen dieser Verordnung in der Praxis. Dafür wurden im empirischen Teil Experten befragt, welche in heilpädagogischen Institutionen angestellt sind. Diese können mit ihrer Expertise die Umsetzung der Verordnung und zukunftsweisende Empfehlungen für die Praxis beurteilen und aussprechen. Die Umsetzung verlief inhaltlich in den Institutionen sehr gut, jedoch tauchen bei der praktischen Arbeit Hürden auf, welche die Einrichtungen auf ihre Art und Weise überwinden müssen, indem sie die Verordnung dem Rahmen entsprechend ausdehnen.This thesis is about the implementation of the performance and remuneration regulation 2015 in the curative education institutions. In particular, this thesis deals with the two areas of adult living and participation in employment in the working world, for short TaB. This thesis gives an overview of the Austrian and Styrian handicap legislation, which are very similar but differ in the details, the definition of general disability and of mental disability and the structure of the performance and remuneration regulation and its two areas of adult living and participation in employment in the working world. Furthermore, the World Health Organization and its classification system, which attempts to develop a generally valid definition of disability with its classification and description, and the National Action Plan on Disability are described. The UN Convention on Disability Equality, which Austria has signed and ratified, is also being described. But working with people with disabilities is not just a matter of regulations, laws or conventions, but also the methodological foundations, such as the normalization principle, the empowerment concept, the self-determination, the participation and the SIVUS method. The main focus, as already mentioned, is the practical implementation of the Regulation, as well as the advantages and problems of this Regulation in practice. For this purpose, the empirical sub-experts were interviewed who are employed in curative education institutions. They can use their expertise to assess and implement the implementation of the regulation and future-oriented recommendations for practice. The implementation has been very good in the institutions, but practical hurdles are emerging which institutions must overcome in their own way by extending the scope of the regulation accordingly.vorgelegt von Agnes Sechterberger, Bakk. philAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinZusammenfassungen in Deutsch und EnglischKarl-Franzens-Universität Graz, Masterarbeit, 2017(VLID)224604

In-hospital glycaemic control: A bittersweet symphony

The presence of three domains of dysglycaemia—hyperglycaemia, hypoglycaemia and increased glucose variability—in acute illness has received quite some attention in the medical literature, especially with regard to their relationship to patient outcomes in different patient populations. However, controlling blood glucose levels in hospitalized patients has yielded both favourable and detrimental effects. Glycaemic control appears to be a complex interplay of various elements, or, metaphorically, ‘a bittersweet symphony’. This thesis focuses on epidemiology, monitoring and treatment of in-hospital dysglycaemia in order to optimize in-hospital glycaemic control. In the critically ill, we found that the presence of diabetes affects the relationship between three out of four measures of glycaemic control and intensive care mortality. Furthermore, we show that subcutaneous continuous glucose monitoring (CGM) is as safe and effective compared to intermittent point-of-care measurements and it reduces nursing workload and costs for glucose control using CGM. A newly developed intra-arterial CGM showed similar (and less promising) accuracy results compared to the subcutaneous CGM. The last part of this thesis focus on the consequences of stress-induced hyperglycaemia on coagulation activation. We examined the effect of the human GLP-1 analogue liraglutide in patients undergoing hip surgery and its influence on coagulation activation. The results show a significant albeit moderate reduction in glucose level (0.3 mmol/L) in patients treated with liraglutide. However, this decrease in glucose level did not convincingly influence coagulation activation. Thus, a causal relation between glucose lowering and altered coagulation activation could not be confirmed

Poor agreement of computerized calculators for mean amplitude of glycemic excursions

Glucose variability has been identified as a predictor of hypoglycemia and has been associated with mortality in critically ill patients without diabetes. A popular metric to quantify glucose variability is the mean amplitude of glycemic excursions (MAGE). The "ruler and pencil" approach to calculate MAGE is operator-dependent and time-consuming for analysis of continuous glucose monitoring data. Therefore, several computer software programs have been developed for the automated calculation of MAGE. The aim of our study was to evaluate the agreement of currently available MAGE calculators when applied to the same set of continuous glucose monitoring (CGM) traces. Four software programs for calculation of MAGE were identified and used to calculate MAGE of 21 CGM traces from seven patients with type 1 diabetes. Subsequently, the median MAGE per calculator was calculated. The correlation between the MAGE calculators was evaluated by Spearman's correlation analysis. Between-group comparison was performed using analysis of variance. The median MAGE (interquartile range) per calculator was 8.7 (7.1-10.7), 6.7 (5.5-8.6), 6.7 (5.2-8.6), and 5.8 (4.3-7.1), which was statistically different overall (P <0.001). The correlation coefficients between the calculators ranged from 0.787 to 0.999. Available computer programs developed to calculate MAGE show varying agreement. Although software programs for the calculation of MAGE would seem attractive to assess glucose variability, their use has limitations by different outcomes, in the absence of a gold standar