Günter Schreier

Design and Evaluation of a Telemonitoring Concept Based on NFC-Enabled Mobile Phones and Sensor Devices

Utilization of information and communication technologies such as mobile phones and wireless sensor networks becomes more and more common in the field of telemonitoring for chronic diseases. Providing elderly people with a mobile-phone-based patient terminal requires a barrier-free design of the overall user interface including the setup of wireless communication links to sensor devices. To easily manage the connection between a mobile phone and wireless sensor devices, a concept based on the combination of Bluetooth and near-field communication technology has been developed. It allows us initiating communication between two devices just by bringing them close together for a few seconds without manually configuring the communication link. This concept has been piloted with a sensor device and evaluated in terms of usability and feasibility. Results indicate that this solution has the potential to simplify the handling of wireless sensor networks for people with limited technical skills.

Noninvasive Rejection Monitoring of Cardiac Transplants Using High Resolution Intramyocardial Electrograms: Initial US Multicenter Experience

Endomyocardial biopsy (EMB) remains the mainstay for the diagnosis of acute cellular rejection in cardiac transplant patients. A noninvasive alternative that would supplant or reduce the number of EMBs would be a highly desirable and cost‐effective tool. To evaluate one potential alternative, a pacemaker with high resolution telemetry capabilities and two fractally coated epimyocardial leads were implanted in 30 patients at five transplant centers during the heart transplant procedure. Ventricular electrograms were recorded during intrinsic and paced activity and digitized to a laptop‐based data acquisition device. Electrograms were recorded at frequent intervals and systematically on days when EMBs were performed. The electrogram data were then transferred via the Internet to a central data processing site. Clinical patient management was blinded to the electrogram results and varied considerably among the five centers. Using EMB together with clinical assessment of the transplant revealed 18 cases of clinically significant rejection beyond postoperative day 27 that required antirejection therapy. The normalized parameter values extracted from the electrogram recordings during pacing (the ventricular evoked response) that were associated with significant rejection were statistically lower (86%± 16% versus 96%± 22%, P < 0.005). The application of a single‐threshold diagnosis model to the parameter values allowed detection of significant rejection with a negative predictive value of 98%. This analysis also showed that as many as 55% of the routine surveillance EMBs could have been eliminated had the pacemaker monitoring technique been used as a screening tool prior to EMB. A prospective study should further define the role of this technique in the detection and management of cardiac transplant patients.

Mobile health (mHealth) based medication adherence measurement – a pilot trial using electronic blisters in diabetes patients

The aim of the present study was to evaluate a mobile health (mHealth) based remote medication adherence measurement system (mAMS) in elderly patients with increased cardiovascular risk treated for diabetes, high cholesterol and hypertension. Cardiovascular risk was defined as the presence of at least two out of the three risk factors: type 2 diabetes, hypercholesterolaemia and hypertension.

QRS detection based ECG quality assessment

Although immediate feedback concerning ECG signal quality during recording is useful, up to now not much literature describing quality measures is available. We have implemented and evaluated four ECG quality measures. Empty lead criterion (A), spike detection criterion (B) and lead crossing point criterion (C) were calculated from basic signal properties. Measure D quantified the robustness of QRS detection when applied to the signal. An advanced Matlab-based algorithm combining all four measures and a simplified algorithm for Android platforms, excluding measure D, were developed. Both algorithms were evaluated by taking part in the Computing in Cardiology Challenge 2011. Each measures accuracy and computing time was evaluated separately. During the challenge, the advanced algorithm correctly classified 93.3% of the ECGs in the training-set and 91.6 % in the test-set. Scores for the simplified algorithm were 0.834 in event 2 and 0.873 in event 3. Computing time for measure D was almost five times higher than for other measures. Required accuracy levels depend on the application and are related to computing time. While our simplified algorithm may be accurate for real-time feedback during ECG self-recordings, QRS detection based measures can further increase the performance if sufficient computing power is available.

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial

BACKGROUND High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. METHODS We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m2) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m2 per day for 4 days, and melphalan 70 mg/m2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of high-dose chemotherapy, at least 24 h after melphalan in patients who received busulfan and melphalan and at least 72 h after carboplatin etoposide, and melphalan. All patients received subsequent local radiotherapy to the primary tumour site followed by maintenance therapy. The primary endpoint was 3-year event-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704716, and EudraCT, number 2006-001489-17. FINDINGS Between June 24, 2002, and Oct 8, 2010, 1347 patients were enrolled and 676 were eligible for random allocation, 598 (88%) of whom were randomly assigned: 296 to busulfan and melphalan and 302 to carboplatin, etoposide, and melphalan. Median follow-up was 7·2 years (IQR 5·3-9·2). At 3 years, 146 of 296 patients in the busulfan and melphalan group and 188 of 302 in the carboplatin, etoposide, and melphalan group had an event; 3-year event-free survival was 50% (95% CI 45-56) versus 38% (32-43; p=0·0005). Nine patients in the busulfan and melphalan group and 11 in the carboplatin, etoposide, and melphalan group had died without relapse by 5 years. Severe life-threatening toxicities occurred in 13 (4%) patients who received busulfan and melphalan and 29 (10%) who received carboplatin, etoposide, and melphalan. The most frequent grade 3-4 adverse events were general condition (74 [26%] of 281 in the busulfan and melphalan group vs 103 [38%] of 270 in the carboplatin, etoposide, and melphalan group), infection (55 [19%] of 283 vs 74 [27%] of 271), and stomatitis (138 [49%] of 284 vs 162 [59%] of 273); 60 (22%) of 267 patients in the busulfan and melphalan group had Bearman grades 1-3 veno-occlusive disease versus 21 (9%) of 239 in the carboplatin, etoposide, and melphalan group. INTERPRETATION Busulfan and melphalan improved event-free survival in children with high-risk neuroblastoma with an adequate response to induction treatment and caused fewer severe adverse events than did carboplatin, etoposide, and melphalan. Busulfan and melphalan should thus be considered standard high-dose chemotherapy and ongoing randomised studies will continue to aim to optimise treatment for high-risk neuroblastoma. FUNDING European Commission 5th Framework Grant and the St Anna Kinderkrebsforschung.

Cardiac anisotropy: is it negligible regarding noninvasive activation time imaging?

The aim of this study was to quantify the effect of cardiac anisotropy in the activation-based inverse problem of electrocardiography. Differences of the patterns of simulated body surface potential maps for isotropic and anisotropic conditions were investigated with regard to activation time (AT) imaging of ventricular depolarization. AT maps were estimated by solving the nonlinear inverse ill-posed problem employing spatio-temporal regularization. Four different reference AT maps (sinus rhythm, right-ventricular and septal pacing, accessory pathway) were calculated with a bidomain theory based anisotropic finite-element heart model in combination with a cellular automaton. In this heart model a realistic fiber architecture and conduction system was implemented. Although the anisotropy has some effects on forward solutions, effects on inverse solutions are small indicating that cardiac anisotropy might be negligible for some clinical applications (e.g., imaging of focal events) of our AT imaging approach. The main characteristic events of the AT maps were estimated despite neglected electrical anisotropy in the inverse formulation. The worst correlation coefficient of the estimated AT maps was 0.810 in case of sinus rhythm. However, all characteristic events of the activation pattern were found. The results of this study confirm our clinical validation studies of noninvasive AT imaging in which cardiac anisotropy was neglected.

Innovative telemonitoring system for cardiology: from science to routine operation.

OBJECTIVE Results of the Austrian MOBITEL (MOBIle phone based TELemonitoring for heart failure patients) trial indicate that home-based telemonitoring improves outcome of chronic heart failure (CHF) patients and reduces both frequency and duration of hospitalizations. Based on lessons learned, we assessed the weak points to clear the way for routine operations. METHODS We analyzed the system with respect to recommendations of the ESC Guidelines and experiences gained throughout the trial to identify potential improvements. The following components have been identified: a patient terminal with highest usability, integrated way to document drug-intake and well-being, and automated event detection for worsening of CHF. As a consequence the system was extended by Near Field Communication (NFC) technology and by an event management tool. RESULTS Usability evaluation with 30 adults (14f, median 51y. IQR[45-65]) showed that 21 (8f) were able to immediately operate the system after reading a step-by-step manual. Eight (6f) needed one time demonstration and one man (80y) failed to operate the blood pressure meter. Routine operation of the revised system started in March 2009. Within 9 months, 15 patients (4f, median 74y. IQR[71-83], all NYHA-III) transmitted 17,149 items. 43 events were detected because of body weight gain of more then 2kg within 2 days. 49 therapy adjustments were documented. Three patients stopped using the system, two (1f) because of non-compliance and one (m, 82y) because of death. Overall, the rate of adherence to daily data transfer was 78%. CONCLUSION First results confirm the applicability of the revised telemonitoring system in routine operation.

A mobile-phone based teledermatology system to support self-management of patients suffering from psoriasis

Psoriasis is one of the most common chronic skin diseases, affecting about 2% of the population world wide. Continuous clinical monitoring with periodic assessment of the state of the disease is essential for long-term therapy optimization. We present a mobile phone based telemedical compliance management system for psoriasis-patients. Using special software, patients can acquire health parameters such as their body weight, take photos of their psoriasis lesions, and report adverse effects. The data are automatically sent to a monitoring centre, where they are provided to the patients physician via the use of a web-browser. In case of therapy relevant events, email or SMS notifications can be sent to the physician. If necessary, the physician can send feedback messages to the patient, e.g. for admitting the patient to the clinic for further examinations. The system has been implemented and functional tests have proven its functionality. Currently, the system is used in the course of a medical case series.

Dynamic simulations on the mitochondrial fatty acid beta-oxidation network.

BackgroundThe oxidation of fatty acids in mitochondria plays an important role in energy metabolism and genetic disorders of this pathway may cause metabolic diseases. Enzyme deficiencies can block the metabolism at defined reactions in the mitochondrion and lead to accumulation of specific substrates causing severe clinical manifestations. Ten of the disorders directly affecting mitochondrial fatty acid oxidation have been well-defined, implicating episodic hypoketotic hypoglycemia provoked by catabolic stress, multiple organ failure, muscle weakness, or hypertrophic cardiomyopathy. Additionally, syndromes of severe maternal illness (HELLP syndrome and AFLP) have been associated with pregnancies carrying a fetus affected by fatty acid oxidation deficiencies. However, little is known about fatty acids kinetics, especially during fasting or exercise when the demand for fatty acid oxidation is increased (catabolic stress).ResultsA computational kinetic network of 64 reactions with 91 compounds and 301 parameters was constructed to study dynamic properties of mitochondrial fatty acid β-oxidation. Various deficiencies of acyl-CoA dehydrogenase were simulated and verified with measured concentrations of indicative metabolites of screened newborns in Middle Europe and South Australia. The simulated accumulation of specific acyl-CoAs according to the investigated enzyme deficiencies are in agreement with experimental data and findings in literature. Investigation of the dynamic properties of the fatty acid β-oxidation reveals that the formation of acetyl-CoA – substrate for energy production – is highly impaired within the first hours of fasting corresponding to the rapid progress to coma within 1–2 hours. LCAD deficiency exhibits the highest accumulation of fatty acids along with marked increase of these substrates during catabolic stress and the lowest production rate of acetyl-CoA. These findings might confirm gestational loss to be the explanation that no human cases of LCAD deficiency have been described.ConclusionIn summary, this work provides a detailed kinetic model of mitochondrial metabolism with specific focus on fatty acid β-oxidation to simulate and predict the dynamic response of that metabolic network in the context of human disease. Our findings offer insight into the disease process (e.g. rapid progress to coma) and might confirm new explanations (no human cases of LCAD deficiency), which can hardly be obtained from experimental data alone.

An Integrated Healthcare Information System for End-to-End Standardized Exchange and Homogeneous Management of Digital ECG Formats

This paper investigates the application of the enterprise information system (EIS) paradigm to standardized cardiovascular condition monitoring. There are many specifications in cardiology, particularly in the ECG standardization arena. The existence of ECG formats, however, does not guarantee the implementation of homogeneous, standardized solutions for ECG management. In fact, hospital management services need to cope with various ECG formats and, moreover, several different visualization applications. This heterogeneity hampers the normalization of integrated, standardized healthcare information systems, hence the need for finding an appropriate combination of ECG formats and a suitable EIS-based software architecture that enables standardized exchange and homogeneous management of ECG formats. Determining such a combination is one objective of this paper. The second aim is to design and develop the integrated healthcare information system that satisfies the requirements posed by the previous determination. The ECG formats selected include ISO/IEEE11073, Standard Communications Protocol for Computer-Assisted Electrocardiography, and an ECG ontology. The EIS-enabling techniques and technologies selected include web services, simple object access protocol, extensible markup language, or business process execution language. Such a selection ensures the standardized exchange of ECGs within, or across, healthcare information systems while providing modularity and accessibility.