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Every year, hundreds of thousands of patients are affected by treatment failure or adverse drug reactions, many of which could be revented by pharmacogenomic testing. To address these deficiencies in care, clinics require
automated clinical decision support through computer based systems, which provide clinicians with patient-specific ecommendations. The primary knowledge needed for clinical pharmacogneomics is currently being
developed through textual and unstructured guidelines.
In this thesis, it is evaluated whether a web service can annotate clinically relevant genetic variants with guideline information using web services and identify areas of challenge. The proposed tool displays a formal representation of pharmacogenomic guideline information through a web service and existing resources. It enables the annotation of variant call format (VCF) files with clinical guideline information from the Pharmacogenomic Knowledge Base (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC).
The applicability of the web service to nnotate clinically relevant variants with pharmacogenomics guideline information is evaluated by translating five guidelines to a web service workflow and executing the process to annotate publically available genomes. The workflow finds genetic variants covered in CPIC guidelines and influenced drugs.
The results show that the web service could be used to annotate in real time clinically relevant variants with up-to-date pharmacogenomics guideline information, although several challenges such as translating variants into star allele nomenclature and the absence of a unique haplotype nomenclature
remain before the clinical implementation of this approach and the use on other drugs.
There are many drug interactions and to know every single interaction is impossible. In Uganda, a country located in East Africa, patients often do not get a patient information leflaet when a physician prescribes drugs because they only get the drugs without packaging and information inside. Even in developed countries many poeple die because of drug interactions.
This work aims at developing a clinical decision support system for different kinds of drug interactions: 1) drug-drug interaction,
2) drug-food interactions,
3) drug-condition
interactions and
4) drug-disease interactions.
This system must be integrated into an
existing hospital information system called electronic Health Management Information System (eHMIS).
In the first part of this thesis different kinds of clinical decision support systems are described to find out which one is the best for eHMIS. The two different types are knowledge-based and non knowledge-based systems. The second part of this thesis, the data base of eHMIS is extended to have a full
knowledge base for the new module which contains drug-drug interactions, drug-food interactions, drug-disease interactions as well as drug-condition interactions. Therefore new tables were created and filled with data of several data bases with drug interactions. The last part is about designing the clinical decision support system for drug interactions
with the knowledge base of eHMIS, including the implementation considering the integration into the existing system. To know how health professionals in Uganda work
with an electronical health system as well as their other work ows was important. The system now runs in a hospital in Kampala, the capital of Uganda and in a health center level three in Mifumi, a village located in the east of the country.
Alzheimer’s Disease affects millions of people worldwide, but till today, the gold standard
for definitive diagnosis of this disease is a biopsy. Nevertheless, with the progress
of the disease, a volume loss in the Hippocampus can be observed. Therefore, good
segmentation methods are crucial to facilitate quantification of this loss.
The focus of this work is on the development of a Machine Learning algorithm, more
precisely a Generative Adversarial Network, for the automated segmentation of the
human Hippocampus and its substructures in Magnetic Resonance Images. In particular,
the task is to determine if the integration of a pre-trained network that generates
segmentations into a Generative Adversarial Network scheme can improve generated
segmentations. In this context, a segmentation network in form of a U-net corresponds
to the generator. The discriminator is developed separately and merged in a second
step with the generator for combined training.
With a literature review regarding the automated segmentation of the Hippocampus,
current methods in this field and their medical and technological basics were identified.
The datasets were preprocessed to make them suitable for the use in a neural
network. In the training process, the generator was trained first until convergence.
Then, the Generative Adversarial Network including the pre-trained generator was
trained. The outcomes were evaluated via cross-validation in two different datasets
(Kulaga-Yoskovitz and Winterburn). The Generative Adversarial Network scheme
was tested regarding different architectural and training aspects, including the usage
of skip-connections and a combined loss function.
The best results were achieved in the Kulaga-Yoskovitz dataset with a Dice coefficient
of 90.84 % after the combined training of generator and discriminator with a joined
loss function. This improves the current state of the art method in the same task and
dataset with a Dice index of 88.79 % by Romero [Rom17]. Except of two cases in the
Winterburn dataset, the proposed combined method could always improve the Dice
results after the training of only the generator, even though only by a small amount.
Ambulant studies are dependent on the behavior and compliance of subjects in their home environment. Especially during interventions on the musculoskeletal system, monitoring physical activity is essential, even for research on nutritional, metabolic, or neuromuscular issues. To support an ambulant study at the German Aerospace Center (DLR), a pattern recognition system for human activity was developed. Everyday activi-ties of static (standing, sitting, lying) and dynamic nature (walking, ascending stairs, descending stairs, jogging) were under consideration. Two tri-axial accelerometers were attached to the hip and parallel to the tibia. Pattern characterizing features from the time domain (mean, standard deviation, absolute maximum) and the frequency domain (main frequencies, spectral entropy, autoregressive coefficients, signal magni-tude area) were extracted. Artificial neural networks (ANN) with a feedforward topology were trained with backpropagation as supervised learning algorithm. An evaluation of the resulting classifier was conducted with 14 subjects completing an activity protocol and a free chosen course of activities. An individual ANN was trained for each subject. Accuracies of 87,99 % and 71,23 % were approached in classifying the activity protocol and the free run, respectively. Reliabilities of 96,49 % and 76,77 % were measured. These performance parameters represent a working ambulant physical activity monitor-ing system.
Implementation of an interactive pattern mining framework on electronic health record datasets
(2019)
Large collections of electronic patient records contain a broad range of clinical information highly relevant for data analysis. However, they are maintained primarily for patient administration, and automated methods are required to extract valuable knowledge for predictive, preventive, personalized and participatory medicine. Sequential pattern mining is a fundamental task in data mining which can be used to find statistically relevant, non-trivial temporal dependencies of events such as disease comorbidities. This works objective is to use this mining technique to identify disease associations based on ICD-9-CM codes data of the entire Taiwanese population obtained from Taiwan’s National Health Insurance Research Database.
This thesis reports the development and implementation of the Disease Pattern Miner – a pattern mining framework in a medical domain. The framework was designed as a Web application which can be used to run several state-of-the-art sequence mining algorithms on electronic health records, collect and filter the results to reduce the number of patterns to a meaningful size, and visualize the disease associations as an interactive model in a specific population group. This may be crucial to discover new disease associations and offer novel insights to explain disease pathogenesis. A structured evaluation of the data and models are required before medical data-scientist may use this application as a tool for further research to get a better understanding of disease comorbidities.
Medication reconciliation is defined by the American Society of Health- System Pharmacists (ASHP) and the American Pharmacists Association (AphA) as “the comprehensive evaluation of a patient’s medication regimen any time there is a change in therapy in an effort to avoid medication errors such as omissions, duplications, dosing errors or drug interactions, as well as to observe compliance and adherence patterns “. Medication reconciliation is very important to avoid medication errors but it is also a complex and time-consuming process. Medication histories, i.e. records of prescription, purchase, and refill sequences are considered to be a resource from which conclusions about medication reconciliation can be drawn. However, medication histories spread across diverse paper and electronic media may lack the required accuracy. By employing multiple electronic sources this thesis will evaluate if more accurate medication histories can be collected.
The Greifswald University Hospital in Germany conducts a research project called "Greifswald Approach to Individualized Medicine (GANI_MED)", which aims at improving patient care through personalized medicine. As a result of this project, there are multiple regional patient cohorts set up for different common diseases. The collected data of these cohorts will act as a resource for epidemiological research. Researchers are going to get the possibility to use this data for their study, by utilizing a variety of different descriptive metadata attributes. The actual medical datasets of the patients are integrated from multiple clinical information systems and medical devices. Yet, at this point in the process of defining a research query, researchers do not have proper tools to query for existing patient data. There are no tools available which offer a metadata catalogue that is linked to observational data, which would allow convenient research. Instead, researchers have to issue an application for selected variables that fit the conditions of their study, and wait for the results. That leaves the researchers not knowing in advance, whether there are enough (or any) patients fitting the specified inclusion and exclusion criteria. The "Informatics for Integrating Biology and the Bedside (i2b2)" framework has been assessed and implemented as a prototypical evaluation instance for solving this issue. i2b2 will be set up at the Institute for Community Medicine (ICM) at Greifswald, in order to act as a preliminary query tool for researchers. As a result, the development of a research data import routine and customizations of the i2b2 webclient were successfully performed. An important part of the solution is, that the metadata import can adapt to changes in the metadata. New metadata items can be added without changing the import program. The results of this work are discussed and a further outlook is described in this thesis.
In this thesis a software system is proposed that provides transparent access to dynamically processed data using a synthetic filesystem for the data transfer as well as interaction with the processing pipeline. Within this context the architecture for such a software solution has been designed and implemented. Using this implementation various profiling measurements have been acquired in order to evaluate the applicability in different data processing scenarios. Usability aspects, considering the interaction with the processing pipeline, have been examined as well. The implemented software is able to generate the processing result on-the-fly without modification of the original input data. Access to the output data is provided by means of a common filesystem interface without the need of implementing yet another communication protocol. Within the processing pipeline the data can be accessed and modified independently from the actual input and output encoding. Currently the data can be modified using a C/C++, GLSL or Java front end. Profiling data has shown that the overhead induced by the filesystem is negligible for most usage patterns and is only critical for realtime processing with a high data throughput e. g. video processing at or above 30 frames per second where typically no file operations are involved.
eHMIS is a Ugandan Hospital Information System (HIS), which targets the Sub-Saharan market. In its first version all forms were programmed statically and adaptations were done by code modifications. In 2014 the development of a second version of eHMIS based on Java started.
This work aims at introducing dynamic forms to this new version. While forms that are significantly important to the workflow of the application will remain static, others are replaced by forms that are dynamically designed by the user. By that, the application will become more flexible and local and situational tailoring will be possible without inducing extra costs.
In this thesis the design, implementation and testing of dynamic forms in eHMIS is discussed. The architecture is based on the questionnaire resource of FHIR®. The module enables the user to create questions and group them into sections and questionnaires. For each question the type of answer expected and other constraints can be defined. A user interface covering all functions was designed, so that no programming skills are required. In a first step dynamic forms were integrated in the application's workflow for recording symptoms, though other fields of application are possible. For testing, a usability experiment was conducted in Tororo Hospital in Eastern Uganda, using the thinking aloud method. Results were analysed and evaluated to detect usability problems and gain a general impression of user satisfaction.
Spinodal Zr0.4Hf0.6Ni1.15Sn half-Heusler thermoelectrics are synthesized and aged. The complex microstructure due to the spinodal decomposition is investigated by powder X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM). By Rietveld refinements, it is confirmed that excess Ni atoms in the arc-melted and spark-plasma-sintered half-Heusler matrix prefer to form nanoscale/ submicron Heusler precipitates via spinodal decomposition and growth during the aging at 1173 K. Such phase separation changes the band gap of semiconductors, reduces the thermal conductivity drastically and improves the performance of thermoelectrics. As a result, a more than 50 % improvement of the ZT value on the unaged specimens was achieved.