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ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity of the [Ca2+]c events persisted throughout the course of T1D development. At the late islet destruction phase, the α-cell [Ca2+]c events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in β-cells and potential α-cells functional synchronization in NOD mice over the course of T1D development.

The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity of the [Ca2+]c events persisted throughout the course of T1D development. At the late islet destruction phase, the α-cell [Ca2+]c events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in β-cells and potential α-cells functional synchronization in NOD mice over the course of T1D development.

Pulmonary hypertension (PH) is a severe hemodynamic, progressive condition associated with high morbidity and mortality where early and less invasive diagnostics could crucially improve management. There is a need for biomarkers in PH that are functional, diagnostic, and prognostic. We used a broad metabolomics approach with machine learning analysis and specific free fatty acid (FFA)/lipid-ratios to develop diagnostic and prognostic PH biomarkers.In a training cohort of 74 PH patients, 30 disease controls without PH, and 65 healthy controls, we identified diagnostic and prognostic markers that were validated in an independent cohort of 64 subjects. Markers based on lipophilic metabolites were more robust than those based on hydrophilic metabolites. FFA/lipid-ratios provided excellent diagnostic accuracy for PH with an AUC of up to 0.89 and 0.90 in the training and the validation cohorts, respectively. The ratios provided age-independent prognostic information and a combination of a ratio with established clinical scores increased the hazard ratio (HR) for FPHR4p and COMPERA2 from 2.5 to 4.3 and from 3.3 to 5.6, respectively.Pulmonary arteries (PA) of idiopathic PAH (IPAH) lungs show lipid accumulation and altered expression of lipid homeostasis-related genes that may explain this accumulation. Our functional studies in PA endothelial and smooth muscle cells have shown that increased FFA levels caused excessive proliferation and PA endothelial barrier dysfunction, both hallmarks of pulmonary artery hypertension (PAH).In conclusion, lipidomic changes in PH provide novel diagnostic and prognostic biomarkers and may point to new metabolic therapy targets.

Summary Background The number of dialysis patients is steadily increasing. Associated comorbidities include impaired bone and mineral metabolism, termed chronic kidney disease-mineral and bone disorder (CKD-MBD), leading to a high fracture risk, increased morbidity and mortality and impaired quality of life. While the bone density is assessed with dual-energy X‑ray absorptiometry (DXA), the trabecular bone score (TBS) captures the image texture as a potential index of skeletal microarchitecture. The aim of this study was to evaluate the clinical relevance of DXA and TBS in dialysis patients with and without prevalent fractures. Methods Bone disorders were evaluated in 82 dialysis patients (37% female) at the University Hospital of Graz, Austria, by DXA including the assessment of the TBS based on a patient interview and the local routine patient database software. The patient cohort was stratified by having sustained a fragility fracture in the past or not. Descriptive statistics, t‑tests for continuous variables and χ2-tests for nominal variables including results of DXA and TBS were performed to compare these groups considering the dialysis modality and duration as well as the number of kidney transplantations. Results Of the 82 patients, 32 (39%) had a positive history of fractures. There was a significant association between dialysis duration and fracture prevalence (p p p Conclusion The use of DXA has a limited role in fracture prediction in dialysis patients; however, the TBS seems to add information as an additional tool for fracture risk estimation in this patient population.

OBJECTIVE To investigate the safety and feasibility of 3 nonconsecutive days of intermittent fasting (IF) per week over 12 weeks in participants with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS Forty-six people were randomized to an IF or control group. Dietary counseling and continuous glucose monitoring was provided. Coprimary end points were the change in HbA1c from baseline to 12 weeks and a composite end point (weight reduction ≥2%, insulin dose reduction ≥10%, and HbA1c reduction ≥3 mmol/mol). RESULTS The IF group showed a significant HbA1c reduction (−7.3 ± 12.0 mmol/mol) compared with the control group (0.1 ± 6.1 mmol/mol) over 12 weeks (P = 0.012). The coprimary end point was achieved by 8 people in the IF and none in the control group (P < 0.001). No severe hypoglycemia occurred. CONCLUSIONS IF is a safe and feasible dietary option to ameliorate glycemic control while reducing total daily insulin dose and body weight in insulin-treated people with type 2 diabetes.

Coronavirus disease 2019 (COVID-19)-induced metabolic alterations have been proposed as a source for prognostic biomarkers and may harbor potential for therapeutic exploitation. However, the metabolic impact of COVID-19 in hemodialysis (HD), a setting of profound a priori alterations, remains unstudied. To evaluate potential COVID-19 biomarkers in end-stage kidney disease (CKD G5), we analyzed the plasma metabolites in different COVID-19 stages in patients with or without HD. We recruited 18 and 9 asymptomatic and mild, 11 and 11 moderate, 2 and 13 severely affected, and 10 and 6 uninfected HD and non-HD patients, respectively. Plasma samples were taken at the time of diagnosis and/or upon admission to the hospital and analyzed by targeted metabolomics and cytokine/chemokine profiling. Targeted metabolomics confirmed stage-dependent alterations of the metabolome in non-HD patients with COVID-19, which were less pronounced in HD patients. Elevated kynurenine levels and lipid dysregulation, shown by an increase in circulating free fatty acids and a decrease in lysophospholipids, could distinguish patients with moderate COVID-19 from non-infected individuals in both groups. Kynurenine and lipid alterations were also associated with ICAM-1 and IL-15 levels in HD and non-HD patients. Our findings support the kynurenine pathway and plasma lipids as universal biomarkers of moderate and severe COVID-19 independent of kidney function.

Breakdown of self-tolerance is an important common mechanism in autoimmunity. We use machine learning (ML) to identify common patterns and dissimilarities between type 1 diabetes (T1D) , rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) based on immune phenotyping. PBMCs were isolated from patients with T1D, RA, SLE, and controls. A FACS approach was applied, and a traditional analysis was compared to a ML method implemented on R and based on self-organizing maps (Fig) . Our pipeline includes unsupervised pre-gating, normalization, FlowSOM clustering, and a statistical model (GLMM) , to check for significant differential abundances of cell populations among the autoimmune conditions. After applying our automated workflow to one T cell panel we could identify 14 new cell clusters present in all the samples. The GLMM test revealed a cluster with a significant difference (p=0.035) and a trending one (p=0.059) on the abundance across the different diseases. In particular, CD4pos T cells expressing high IL-7 receptor (CD127) levels and median amounts of CD15s but low CD25, CD161 and FoxP3 are increased in T1D whereas CD4+CD25++CD15s+FoxP3lowCD161lowCD45RA- cells are increased in SLE. In conclusion, our ML workflow identifies a new subtype of T cells significantly increased in T1D. This unsupervised analysis approach for large datasets enables the discovery of new biomarkers complementing traditional workflows. Disclosure J.Vera-ramos: None. B.Prietl: None. L.Herbsthofer: None. V.Pfeifer: None. P.López-garcía: None. M.Stradner: Consultant; AbbVie Inc., AstraZeneca, Speaker's Bureau; Janssen Pharmaceuticals, Inc. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Research Support; AstraZeneca, European Union, JDRF, Novo Nordisk Foundation, Sanofi, Speaker's Bureau; Novo Nordisk A/S, Roche Diagnostics. Funding JDRF, LRA, & NMSS Joint RFA (2-SRA-2021-1043-S-B)

Insulin icodec is a basal insulin in development for once-weekly (OW) dosing. The aim of this study was to compare the hypoglycemia frequency and response after icodec vs. insulin glargine U100 (IGlar) overdosing. In a randomized, open-label, two-period crossover trial, 43 individuals with T2D on basal insulin±metformin (mean±SD age 56±9 yrs, HbA1c 7.2±0.7%) received OW icodec for 6 weeks and once-daily IGlar for 12 days at equimolar total weekly doses based on the individual daily run-in IGlar dose (mean 30±14 U) titrated to a fasting SMPG target of 80-130 mg/dL. Once at steady state, double (DD) and triple (TD) doses of icodec and IGlar were followed by hypoglycemia induction 44 h (icodec) or 7 h (IGlar) post-dose (expected time of maximum glucose-lowering effect) : First, euglycemia was maintained at 100 mg/dL by variable i.v. glucose. Then, PG was allowed to decrease to a nadir of no less than 45 mg/dL maintained for 15 min. Euglycemia was restored by constant i.v. glucose. Hypoglycemic symptom score (HSS) and counterregulatory hormones were assessed at PG 100 mg/dL and at predefined PG levels until nadir PG. For DD, clinically significant hypoglycemia (PG In conclusion, a DD or TD of once-weekly insulin icodec does not lead to increased risk of hypoglycemia compared to once-daily IGlar. During hypoglycemia, a comparable symptomatic response and a moderately greater endocrine response were seen for icodec vs. IGlar. Disclosure E.Svehlikova: n/a. K.Niss arfelt: Employee; Novo Nordisk. R.Cailleteau: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. S.Deller: None. K.Thomsen: Employee; Novo Nordisk. M.Hart: None. I.Mursic: None. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Research Support; AstraZeneca, European Union, JDRF, Novo Nordisk Foundation, Sanofi, Speaker's Bureau; Novo Nordisk A/S, Roche Diagnostics. H.Haahr: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. Funding Novo Nordisk

Background: Medication errors are common in hospitals. Our aim was to investigate risks of the analogue and digitally-supported medication use process and potential for solutions.Methods: A mixed-method study including a structured literature search, and questionnaires based on the Delphi method was conducted. To identify major risks, a literature search was supplemented by risks from Critical-Incident-Reporting-System cases and risks from experts’ know-how. First, all risks were structured into main and sub-risks and second, risks were grouped into risk clusters. Third, experts were asked to assess risk clusters regarding likelihood of occurrence and impact on patient safety and regarding potential for solutions to strengthen the competence of health care professionals and potential for solutions in digitalization.Results: Overall, 160 main risks and 542 sub-risks were identified. Main risks were grouped into 43 risk clusters. In total, 33 experts (56% female, 50% with >20 years professional-experience) ranked the likelihood of occurrence and the impact on patient safety to 15 top risk clusters regarding the following process steps: admission (n=4), prescribing (n=3), verifying (n=1), preparing/dispensing (n=3), administering (n=1), discharge (n=1), health care professional competence (n=1), and patient (n=1). In total 28 experts (64% female, 43% with >20 years professional-experience) mostly suggested awareness building and training, strengthening of networking, and involvement of pharmacists at point-of-care as solutions to strengthen health care professional competence. For solutions in digitalization a digital medication list, digital warning systems, barcode-technology, and digital support in integrated care were suggested.Conclusions: A multitude of different risks was identified in the medication use process. To increase patient safety and to minimize potential errors, different solutions to strengthen health care professional competence as well as digital solutions exist. As a next step, health care professional competence and digital solutions will be investigated more deeply to derive specific recommendations for intra-hospital clinical practice use.

BACKGROUND AND AIMS Patients on haemodialysis (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and decreased ICU admissions when hospitalized with COVID-19. It was speculated that an altered immune system due to chronic inflammation might protect HD patients from severe COVID-19. Therefore, we designed a study to describe the peripheral blood immune phenotype in HD patients and respective controls with COVID-19. METHOD Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild and moderate/severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping were performed. RESULTS Th1 and Th17 plasma cytokine levels were highly increased in HD patients without SARS-CoV-2 infection and were not significantly regulated during COVID-19. In non-HD COVID-19 patients, these cytokines increased significantly with disease severity. While all patients with moderate/severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+ CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in HD compared to non-HD patients with moderate/severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients. Significantly fewer moderate/severe COVID-19 HD patients needed ICU treatment [1/13 (7.7%) HD, 12/24 (50%) non-HD], whereas no difference in mortality was observed [4/31 (12.9%) HD, 6/33 non-HD (18.2%)]. CONCLUSION HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.

BACKGROUND In precision oncology ex vivo drug screening systems have the potential to improve clinical outcomes. Traditionally, cancer drugs are tested on cancer cell line models, but these cannot represent an individual patient and are biologically too distinct. Drug screening systems usually rely on viability assays and correlations to genomic alterations. Beside genomic alterations, the cellular metabolism is significantly altered which may lead to drug resistance. Here we aim to establish a drug screening platform using tumor cells derived directly from the individual patient glial tumor tissue, create patient derived tumor cells (PDCs) and combine the outcomes from standardized viability- and genetic-assays with a new developed metabolomics platform. Materials and METHODS Fresh native tissue from patients harbouring low- and high-grade glioma are collected (n=46). Tumor tissue used for NMR-based metabolomic analyses and targeted sequencing analyses as well as PDC isolation. To preserve the original tumor similarity, tissue is short term cultured for two weeks, and PDCs are seeded and treated with a panel of clinical- and preclinical drugs followed by viability assessment, sequencing and metabolomic profiling. RESULTS Culturing of PDCs is successful in ≥ 85% of patient cases, provided that at least 2 g of tumor tissue is available. The automatized high throughput ex vivo drug response identifies drug candidates, which might become relevant for therapeutic approaches in future. It is possible to distinguish between IDH1-wild-type and IDH1-mutant tumors based on the metabolomic profile, which is confirmed by immunohistochemical staining and molecular analysis of IDH1 R132H-mutation. Strong metabolomic variations have been identified, including GABA, lactate, and myo-inositol levels between tumor and healthy tissue. CONCLUSION Entangling drug screening and genetic assays with metabolomic profiling of glial tumors enriches the information about cellular drug response and paves the way for future clinical studies and better understanding of underlying drug resistance mechanisms in gliomas.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

Recent incidents have shown that sensor-equipped devices can be used by adversaries to perform malicious activities, such as spying on end-users or for industrial espionage. In this paper, we present a novel attack scenario that uses unsecured embedded sensors to build covert channels that can be used to bypass security mechanisms and transfer information between isolated processes. We present covert channels that require read- and write-access for sensor registers as well as a covert channel that transfers data by just triggering sensor readings so that malicious behavior cannot be distinguished from normal sensor usage. For each presented covert channel we discuss the trade-off between data rate and the likelihood of being detected as well as potential countermeasures. The fastest covert channel we implemented achieves a data rate of 4844 bit/s while the stealthiest but slower covert channel cannot be distinguished from normal user behavior. To highlight the significance of these security issues, we used popular platforms, such as Linux and Android, to evaluate the presented covert channels. However, we do not make any assumption regarding the device’s platform, and thus we believe that the presented exploits pose a significant security risk for any sensor-equipped device.

In modern society sensors are omnipresent. They gather information about their environment in order to optimize production flows, minimize energy usage, learn about the environment, or maximize the owner’s comfort. To achieve the desired goal in already existing buildings, sensors are introduced afterwards. These sensors might not be able to connect to a sensor network because of obstacles or user policies. If this happens, other mechanisms to create a network to gather the data need to be found. Additionally, these sensors should last for a long period and are therefore probably powered using energy harvesting methods. In this paper we present an approach for simulating the charging process of such sensors and connecting them to a network using mobile communication partners.

BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (PCONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).

High tech strategies such as Industry 4.0 and Smart Manufacturing require industrial devices to be connected to the Internet. This movement towards interconnected industrial devices poses significant security risks as confidential data must be transferred and stored using untrustworthy channels and cloud servers. End-to-end private key cryptography is suitable to protect the confidentiality, integrity, and authenticity of data. However, private key cryptography has some drawbacks such as the so-called key distribution problem. A possible solution, factory installed keys, are untrustworthy as the two partners relying on end-to-end cryptography can not be sure that no other party is in possession of the used keys. To overcome these problems, the Bring Your Own Key (BYOK) principle based on Near Field Communication (NFC) and dedicated secured hardware is presented in this paper.

In smart factories and smart homes, devices such as smart sensors are connected to the Internet. Independent of the context in which such a smart sensor is deployed, the possibility to change its configuration parameters in a secure way is essential. Existing solutions do provide only minimal security or do not allow to transfer arbitrary configuration data. In this paper, we present an NFC- and QR-code based configuration interface for smart sensors which improves the security and practicability of the configuration altering process while introducing as little overhead as possible. We present a protocol for configuration as well as a hardware extension including a dedicated security controller (SC) for smart sensors. For customers, no additional hardware other than a commercially available smartphone will be necessary which makes the proposed approach highly applicable for smart factory and smart home contexts alike.

Sensors are a vital component for the Internet of Things. These sensors gather information about their environment and pass this information to control algorithms and/or actuators. To operate as effective as possible the sensors need to be reconfigurable, which allows the operators to optimize the sensing activities. In this work we focus on the mechanisms of such reconfiguration possibilities. As the reconfiguration can also be used to manipulate the sensors (and their attached systems) in a subtle way, the security of the reconfiguration interface is of utmost importance. Within this work we test a lightweight authentication method for use on a smart sensor and describe a possible implementations of the authentication mechanism on a hardware security module.

Public awareness regarding security aspects in the Internet of Things (IoT) is currently rising due to regular media presence of various IoT-related security breaches. One of the major weaknesses of IoT devices is the absence of appropriate mechanisms for firmware and configuration updates. In addition, improved security concepts often result in poor usability which discourages users from relying on these concepts. Therefore, in this paper, we present an easy-to-use NFC-based configuration approach for IoT devices that is secured by appropriate security measures in software and hardware. Since industrial usage of such a configuration approach entails different requirements than home usage, we present and compare three different configuration processes. The applicability of our approach is demonstrated by two prototypical implementations, as well as a detailed security analysis. We also show that the imposed overhead due to the implemented security measures is negligible for most configuration updates.

The necessity to (re-)configure Internet of Things devices such as smart sensors during their entire lifecycle is becoming more important due to recent attacks targeting these devices. Allowing configuration parameters to be changed in any phase of a smart sensor's lifecycle allows security updates or new key material to be applied. Also, the functionality of a smart sensor can be altered by changing its configuration. The challenges that need to be considered when enabling the configuration of arbitrary parameters are the security and usability of the configuration interface, the secured storage of confidential configuration data, and the attestation of successfully applied configuration updates. Therefore, we present an NFC-based configuration approach that relies on dedicated secured hardware to solve these challenges. In addition to a hardware extension for smart sensors, we also present a secured configuration protocol as well as a two-layer configuration attestation process to verify the correct utilization of all transmitted configuration parameters.

A b s t r ac t Background To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. Methods We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P

A1 Meet the needs: Important questions for ICU relatives Magdalena M. Hoffmann1,2, Anna K. Holl3, Harald Burgsteiner4, Thomas Pieber1,5, Philipp Eller6, Karin Amrein1 A2 Daily use of the Surgical Safety Checklist: results of a real-time audit Gerald Sendlhofer1,2,3, Karina Leitgeb1, Veronika Gombotz1, Peter Tiefenbacher1, Lars-Peter Kamolz2,3 A3 Best-practice projects concerning patient safety in Austria Gerald Sendlhofer1,2,3,4, , Karina Leitgeb1,4, Magdalena Hoffmann1,4, Sabine Papst1,4, Susanne Gasteiner1,4, Lars Peter Kamolz2,3,4 A4 Comprehensive Cancer Center Graz: evaluation of availability of mandatory healthcare professionals in tumorboards Peter Tiefenbacher1,2, Yvonne Muller1,2, Gerald Sendlhofer1,2,3,4 A5 Comprehensive Cancer Center Graz: protocol to evaluate communication and recommendation finding in tumorboards Marlies Hart1, Peter Tiefenbacher1,2, Yvonne Muller1,2, Gerald Sendlhofer1,2,3,4 A6 Generating a new insulin prescription chart at a university hospital Julia Kopanz1, Katharina M. Neubauer1, Gerald Sendlhofer2,3,4, Barbara Semlitsch1, Andres Pak5, Gerald Cuder1, Thomas R. Pieber1, Johannes Plank6 A7 The Speech and Language Therapy teaching practice at the Institute for Speech and Language Therapy at FH JOANNEUM in Graz Annemarie Schinko1, Angelika Rother1 A8 Development and implementation of a progress test in undergraduate dental education: a prospective Austrian pilot project Barbara Kirnbauer1, Petra Rugani1, Norbert Jakse1, Johannes Bernhardt-Melischnig2, Rudolf Egger3 A9 What they need and what they get: protocol to identify the needs of information of patients and what they receive so far Magdalena M. Hoffmann1,2, Karina Leitgeb1,3, Esther Trampusch4,5, Angelika Hofer4, Regina Riedl6, Karin Amrein2, Christa Tax7, Gernot Brunner7, Gerald Sendlhofer,1,3,8 A 10 Medication-related problems resolved and money saved: results of a clinical pharmacy service evaluation in the surgical setting Emilie Tudela-Lopez1, Petra Polzleitner1, Klara Jadrna1, Christina Labut1, Maria Kundracikova1, Helga Fend1, Gunar Stemer1 A 11 Intercultural communication management in radiology Jutta Maria Lorenz1 A 12 Spotlight on data quality: comparison of data input by physicians vs. non-physicians in the German Resuscitation Registry Gerhard Prause1, Paul Zajic1, Philipp Zoidl1, Geza Gemes1 A 13 MRSA prevalence and eradication with octenidine Gerald Pichler1, Christian Pux1, Rita Babeluk2, Brigitte Hermann3, Eric Stoiser3, Antonella De Campo4, Andrea Grisold5, Ines Zollner-Schwetz6, Robert Krause6, Walter Schippinger4 A 14 QUIPS: a pain registry with impact in science and daily routine work Alexander Avian1,2, Brigitte Messerer3, Claudia Weinmann2, Winfried Meisner2 A 15 Patient empowerment for the youngest Karina Leitgeb1, Magdalena Hoffmann1, Gerald Sendlhofer1,2,3 A 16 Development of a pocket guide for parenteral nutrition in hospitalized adults Anna Maria Eisenberger1, Siegrid Fuchs2 A 17 Safety and efficacy of a clinical decision support system for blood glucose management in patients with diabetes mellitus type 2 at a plastic-surgical ward Alexandru-C. Tuca1, Katharina M. Neubauer2, Julia K. Mader2, Felix Aberer2 , David B. Lumenta1, Birgit Bauer1 ,Klaus Donsa3 , Thomas Augustin3 , Bernhard Holl3 , Lukas Schaupp2, Peter Beck4, Johannes Plank2 , Thomas R. Pieber2,3, Lars-P. Kamolz1,5 A 18 Urban dwellers show higher readiness in participating actively in the shaping of the healthcare system in Austria Christian Smolle1, Frederike Reischies2, Gudrun Pregartner3, Daryousch Parvizi2, Gerald Sendlhofer1,4, Lars-Peter Kamolz1,4

The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P, Novo Nordisk; National Institutes of Health; LEADER ClinicalTrials.gov