Interoperability Is a Process - The Data Sharing Framework.

Common syntax and data semantics are core components of healthcare interoperability standards. However, interoperable data exchange processes are also needed to enable the integration of existing systems between organizations. While solutions for healthcare delivery processes are available and have been widely adopted, support for processes targeting bio-medical research is limited. Our Data Sharing Framework creates a platform to implement research processes like cohort size estimation, reviews and approvals of research proposals, consent checks, record linkage, pseudonymization and data sharing across organizations. The described framework implements a distributed business process engine for executing BPMN 2.0 processes with synchronization and data exchange using FHIR R4 resources. Our reference implementation has been rolled out to 38 organizations across three research consortia in Germany and is available as open source under the Apache 2.0 license.

Challenge of Detecting Personal Deviations and Trends in Sensor Based Activity Data.

INTRODUCTION: Physical activity and health are closely linked. Therefore, monitoring movement behavior is of great interest e.g., to monitor a patient's physical state. Nowadays it is easy to record movement with a smartphone. The aim of this work was to develop a concept to detect trends based on personalized movement behavior recorded with a smartphone. METHODS: A first prototype with a control chart was designed. Since this approach did not prove suitable for analyzing activity data for trends in practice, a second prototype was subsequently developed with a statistical trend test (Mann-Kendall test (MK test)). It was extended by the Yue-Wang correction approach to be able to deal effectively with serial correlation. Furthermore, the traditional trend modeling using Theil-Sen slope was extended by three additional models to be able to represent non-linear trend shapes. RESULTS: Movement behavior can be highly variable, which leads to wide control limits when using control charts. As the lower control limit was always in the negative range the use of a control chart was impossible for this use case. The evaluation results of the second prototype confirm the choice of a non-parametric test, as well as the decision for the Yue-Wang correction factor. Furthermore, it could be determined that the MK test is robust against outliers. The number of detected trends increases with increasing significance level. The MK test is also suitable for detecting step-like trends. CONCLUSION: Live trend detection is not straightforward with the MK test but can be simulated by overlapping time periods. In the future, trend modeling should be extended even further, as it plays a major role in the concept. The sensitivity of the test can be increased by means of various parameters.

User-Centered Development of a Mobile App to Assess the Quality of Life of Patients With Cancer: Iterative Investigation and Usability Testing.

BACKGROUND: The treatment for cancer can have a negative impact not only on physical well-being but also on mental health and the quality of life (QoL). Health apps enable the monitoring of different parameters, but to date, there are only few that support patients with cancer and none that focuses on the assessment of QoL. Furthermore, patients as stakeholders are often only integrated at the late stage of the development process, if at all. OBJECTIVE: The aim of this research was to develop and evaluate a smartphone app (Lion-App) to enable patients with cancer to autonomously measure the QoL with an iterative, user-centered approach. METHODS: Patients with cancer were involved in a 3-stage process from conceptualization to the point when the app was available on the tester's private device. First, focus groups with members (N=21) of cancer support groups were conducted to understand their expectations and needs. Thereafter, individual tests were performed. After developing a prototype that incorporated findings from the focus groups, a second test cycle was conducted, followed by a beta test lasting 2 months. In our app, the QoL can be assessed via a patient diary and an integrated questionnaire. Through all stages, usability was evaluated using the modular extended version of the User Experience Questionnaire (UEQ+), including the calculation of a key performance indicator (KPI). If possible, the impact of sex on the results was evaluated. As part of the beta test, usage rates as well as age-dependent differences were also assessed. RESULTS: A total of 21 participants took part in the initial 3 focus groups. In the subsequent usability testing (N=18), 17 (94%) participants rated their impression through the UEQ+, with a mean KPI of 2.12 (SD 0.64, range: -3 to 3). In the second usability test (N=14), the mean KPI increased to 2.28 (SD=0.49). In the beta test, the usage rate of 19 participants was evaluated, of whom 14 (74%) also answered the UEQ+ (mean KPI 1.78, SD 0.84). An influence of age on the number of questionnaire responses in Lion-App was observed, with a decrease in responses with increasing age (P=.02). Sex-dependent analyses were only possible for the first usability test and the beta test. The main adjustments based on user feedback were a restructuring of the diary as well as integration of a shorter questionnaire to assess the QoL. CONCLUSIONS: The iterative, user-centered approach for development and usability testing resulted in positive evaluations of Lion-App. Our app was rated as suitable for everyday use to monitor the QoL of patients with cancer. Initial results indicated that the sex and age of participants seem to play only a minor role.

No Transfer Without Validation: A Data Sharing Framework Use Case.

Availability and accessibility are important preconditions for using real-world patient data across organizations. To facilitate and enable the analysis of data collected at a large number of independent healthcare providers, syntactic- and semantic uniformity need to be achieved and verified. With this paper, we present a data transfer process implemented using the Data Sharing Framework to ensure only valid and pseudonymized data is transferred to a central research repository and feedback on success or failure is provided. Our implementation is used within the CODEX project of the German Network University Medicine to validate COVID-19 datasets at patient enrolling organizations and securely transfer them as FHIR resources to a central repository.

Assessing Quality of Life Using FHIR - How to Combine Patient Reported Outcome with Patient Generated Data for Better Compliance.

Quality of life (QoL) is affected by environmental influences and varies between patients. A combined measurement through Patient Reported Outcomes (PROs) and Patient Generated Data (PGD) may enhance the detection of QoL impairments by a longitudinal survey. Leveraging different approaches of QoL measurement techniques, the challenge is to combine data in a standardized, interoperable way. We developed an app (Lion-App) to semantically annotate data from sensor systems as well as PROs to be merged in an overall analysis of QoL. A FHIR implementation guide was defined for a standardized assessment. To access sensor data the interfaces of Apple Health or Google Fit are used instead of integrating various provider directly into the system. Since QoL cannot be collected exclusively via sensor values, a combination of PROs and PGD is necessary. PGD enable a progression of QoL which offers more insight into personal limitations whereas PROs give insight about personal burden. The use of FHIR enables structured exchange of data while personalized analyses might improve therapy and outcome.

Monitoring Distributed Business Processes in Biomedical Research.

In biomedical research, business processes, such as data-sharing or feasibility queries, span across several healthcare organizations. Due to the growing number of data-sharing projects and connected organizations, the management of distributed processes gets more complex over time. This leads to an increased need for administrating, orchestrating, and monitoring all distributed processes of a single organization. A proof of concept for a decentralized and use case agnostic monitoring dashboard was developed for the Data Sharing Framework, which most German university hospitals have deployed. The implemented dashboard can handle current, changing, and upcoming processes using only information for cross-organizational communication. This differentiates our approach from other existing use case specific content visualizations. The presented dashboard is a promising solution to provide administrators with an overview of the status of their distributed process instances. Therefore, this concept will be further developed in upcoming releases.

Secure Multi-Party Computation Based Distributed Feasibility Queries - A HiGHmed Use Case.

The integration of routine medical care data into research endeavors promises great value. However, access to this extra-domain data is constrained by numerous technical and legal requirements. The German Medical Informatics Initiative (MII) - initiated by the Federal Ministry of Research and Education (BMBF) - is making progress in setting up Medical Data Integration Centers to consolidate data stored in clinical primary information systems. Unfortunately, for many research questions cross-organizational data sources are required, as one organization's data is insufficient, especially in rare disease research. A first step, for research projects exploring possible multi-centric study designs, is to perform a feasibility query, i.e., a cohort size calculation transcending organizational boundaries. Existing solutions for this problem, like the previously introduced feasibility process for the MII's HiGHmed consortium, perform well for most use cases. However, there exist use cases where neither centralized data repositories, nor Trusted Third Parties are acceptable for data aggregation. Based on open standards, such as BPMN 2.0 and HL7 FHIR R4, as well as the cryptographic techniques of secure Multi-Party Computation, we introduce a fully automated, decentral feasibility query process without any central component or Trusted Third Party. The open source implementation of the proposed solution is intended as a plugin process to the HiGHmed Data Sharing Framework. The process's concept and underlying algorithms can also be used independently.

The COVID-19 Data Exchange Platform of the German University Medicine.

COVID-19 has challenged the healthcare systems worldwide. To quickly identify successful diagnostic and therapeutic approaches large data sharing approaches are inevitable. Though organizational clinical data are abundant, many of them are available only in isolated silos and largely inaccessible to external researchers. To overcome and tackle this challenge the university medicine network (comprising all 36 German university hospitals) has been founded in April 2020 to coordinate COVID-19 action plans, diagnostic and therapeutic strategies and collaborative research activities. 13 projects were initiated from which the CODEX project, aiming at the development of a Germany-wide Covid-19 Data Exchange Platform, is presented in this publication. We illustrate the conceptual design, the stepwise development and deployment, first results and the current status.

Data Sharing in Distributed Architectures - Concept and Implementation in HiGHmed.

Medical routine data has the potential to benefit research. However, transferring this data into a research context is difficult. For this reason Medical Data Integration Centers are being established in German university hospitals to consolidate data from primary information systems in a single location. But, small data-sets from one organization can be insufficient to answer a research question adequately. In order to obtain larger data-sets, attempts to merge and provide data-sets across institutional boundaries are made. Therefore, this paper proposes a possible process that can extract, merge, pseudonymize and provide distributed data-sets from several organizations conforming to privacy regulations. This process is executed according to the open standard BPMN 2.0, the underlying process data model is based on HL7 FHIR R4. The proposed solution is currently being deployed at eight university hospitals and one Trusted Third Party in the HiGHmed consortium.

Quality of Life as an Indicator for Care Delivery in Clinical Oncology Using FHIR.

INTRODUCTION: Health-related quality of life (HR-QoL) as a parameter for patient well-being is becoming increasingly important.[1] Nevertheless, it is mainly used as an endpoint in studies rather than as an indicator for adjustments in therapy. In this paper we will present an approach to gradually integrate quality of life (QoL) as a control element into the care delivery of oncology. CONCEPT: Acceptance, usability, interoperability and data protection were identified and integrated as key indicators for the development. As an initial approach, a questionnaire tool was developed to provide patients a simplified answering of questionnaires and physicians a clearer presentation of the results. IMPLEMENTATION: As communication standard HL7 FHIR was used and known security concepts like OpenID Concept were integrated. In a usability study, first results were achieved by asking patients in the waiting room to answer a questionnaire, which will be discussed with the physician in the appointment. This study was conducted in 2019 at theSLK Clinics Heilbronn and achieved 86% participation of all respondents with an average age of 67 years. DISCUSSION: Although the evaluation study could prove positive results in usability and acceptance, it is necessary to aim for longitudinal surveys in order to include QoL as a control element in the therapy. However, a longitudinal survey through questionnaires leads to decreasing compliance and increasing response bias. [2] For this reason, the concept needs to be expanded. With sensors a continuous monitoring can be carried out and the data can be mapped to the individual, interpreted by machine learning. CONCLUSION: Questionnaires are a concept that has been successfully applied in studies for years. However, since care delivery poses different challenges, the integration of new concepts is inevitable. The authors are currently working on an extension of the use of questionnaires with patient generated data through sensors.

Executing Distributed Healthcare and Research Processes - The HiGHmed Data Sharing Framework.

Several standards and frameworks have been described in existing literature and technical manuals that contribute to solving the interoperability problem. Their data models usually focus on clinical data and only support healthcare delivery processes. Research processes including cross organizational cohort size estimation, approvals and reviews of research proposals, consent checks, record linkage and pseudonymization need to be supported within the HiGHmed medical informatics consortium. The open source HiGHmed Data Sharing Framework implements a distributed business process engine for executing arbitrary biomedical research and healthcare processes modeled and executed using BPMN 2.0 while exchanging information using FHIR R4 resources. The proposed reference implementation is currently being rolled out to eight university hospitals in Germany as well as a trusted third party and available open source under the Apache 2.0 license.

Feasibility Queries in Distributed Architectures - Concept and Implementation in HiGHmed.

Medical routine data promises to add value for research. However, the transfer of this data into a research context is difficult. Therefore, Medical Data Integration Centers are being set up to merge data from primary information systems in a central repository. But, data from one organization is rarely sufficient to answer a research question. The data must be merged beyond institutional boundaries. In order to use this data in a specific research project, a researcher must have the possibility to query available cohort sizes across institutions. A possible solution for this requirement is presented in this paper, using a process for fully automated and distributed feasibility queries (i.e. cohort size estimations). This process is executed according to the open standard BPMN 2.0, the underlying process data model is based on HL7 FHIR R4 resources. The proposed solution is currently being deployed at eight university hospitals and one trusted third party across Germany.

A Federated Record Linkage Algorithm for Secure Medical Data Sharing.

The process of consolidating medical records from multiple institutions into one data set makes privacy-preserving record linkage (PPRL) a necessity. Most PPRL approaches, however, are only designed to link records from two institutions, and existing multi-party approaches tend to discard non-matching records, leading to incomplete result sets. In this paper, we propose a new algorithm for federated record linkage between multiple parties by a trusted third party using record-level bloom filters to preserve patient data privacy. We conduct a study to find optimal weights for linkage-relevant data fields and are able to achieve 99.5% linkage accuracy testing on the Febrl record linkage dataset. This approach is integrated into an end-to-end pseudonymization framework for medical data sharing.

Evaluating Online Consumer Medication Information Systems: Comparative Online Usability Study.

BACKGROUND: Medication is the most common intervention in health care, and the number of online consumer information systems within the pharmaceutical sector is increasing. However, online consumer information systems can be a barrier for users, imposing information asymmetries between stakeholders. OBJECTIVE: The objective of this study was to quantify and compare the usability of an online consumer medication information system (OCMIS) against a reference implementation based on an interoperable information model for patients, physicians, and pharmacists. METHODS: Quantitative and qualitative data were acquired from patients, physicians, and pharmacists in this online usability study. We administered 3 use cases and a post hoc questionnaire per user. Quantitative usability data including effectiveness (task success), efficiency (task time), and user satisfaction (system usability scale [SUS]) was complemented by qualitative and demographic data. Users evaluated 6 existing systems and 1 reference implementation of an OCMIS. RESULTS: A total of 137 patients, 81 physicians, and 68 pharmacists participated in this study. Task success varied from 84% to 92% in patients, 66% to 100% in physicians, and 50% to 91% in pharmacists. Task completion time decreased over the course of the study for all but 2 OCMIS within the patient group. Due to an assumed nonnormal distribution of SUS scores, within-group comparison was done using the Kruskal-Wallis test. Patients showed differences in SUS scores (P=.02) and task time (P=.03), while physicians did not have significant differences in SUS scores (P=.83) and task time (P=.72). For pharmacists, a significant difference in SUS scores (P<.001) and task time (P=.007) was detected. CONCLUSIONS: The vendor-neutral reference implementation based on an interoperable information model was proven to be a promising approach that was not inferior to existing solutions for patients and physicians. For pharmacists, it exceeded user satisfaction scores compared to other OCMIS. This data-driven approach based on an interoperable information model enables the development of more user-tailored features to increase usability. This fosters data democratization and empowers stakeholders within the pharmaceutical sector.

Development and initial Experience of an online Exchange Platform on Sex and Gender Aspects in Medicine: "GenderMed-Wiki".

Goal: Knowledge about sex/gender aspects in medicine is often lacking, even though this serves as base for individualized patient-centered care. Thus we developed an online exchange platform on sex and gender aspects in medicine: "GenderMed-Wiki" [www.gendermed-wiki.de]. This was funded by the German Federal Ministry of Education and Research (BMBF; FKZ: 01FP1506). Our goal is to facilitate the integration of sex and gender in all areas of medicine. Therefore we evaluated if "GenderMed-Wiki" is suitable to provide knowledge on sex and gender aspects in medicine adequately. Methods: Qualitative evaluation of "GenderMed-Wiki" was done 6 months after project start by 4 focus groups with a total of 30 participants (students, lecturers, physicians, and the public). The discussions in each focus group were minuted, requirements pooled and new categories derived inductively. After further optimization of the platform a quantitative survey was done by an online questionnaire (SoSci Survey). 149 students of the medical faculties of Muenster and Duisburg-Essen (as well as students of dentistry from the medical faculty of Muenster) participated (return rate of 3.3%). Evaluation of the content of the articles was done by assessing three professional articles: Sex/gender and medicine (both study courses medicine and dentistry), depression (medicine only) and periodontitis (dentistry only). The results were reported in relative and absolute frequencies and associations were assessed by Chi-Quadrat-tests. Results: Four categories which needed further optimization were deducted from the responses given by our focus groups prior to evaluation: aspects related to content, technical requirements, usability of the platform and legal challenges. Most of the students found "GenderMed-Wiki" to be informative, however they didn´t think it to be relevant for their current studies. In contrast, many thought that the platform may be useful when working as physicians. Students who reported that topics related to sex and gender were not of importance to them, evaluated the platform more neutrally and answered questions related to sex/gender in depression more often incorrectly. Conclusions: Focus groups are a useful approach to identify necessary changes in projects in a systematic way. After further optimizations, "GenderMed-Wiki" seems to be suitable to facilitate the integration of sex/gender into medical teachings. It is of importance, however, to change the attitude of students towards sex/gender sensitive medicine (e.g. by integration into the medical curriculum), since this influences strongly how this platform is perceived and how someone deals with its contents.

Staphylococcus aureus from the German general population is highly diverse.

OBJECTIVES: This prospective cohort study evaluates colonization dynamics and molecular characteristics of methicillin-susceptible and - resistant Staphylococcus aureus (MSSA/MRSA) in a German general population. METHODS: Nasal swabs of 1878 non-hospitalized adults were screened for S. aureus. Participants were screened thrice in intervals of 6-8 months. Isolates were characterized by spa and agr typing, mecA and mecC possession, respectively, and PCRs targeting virulence factors. RESULTS: 40.9% of all participants carried S. aureus at least once while 0.7% of the participants carried MRSA (mainly spa t011). MSSA isolates (n=1359) were associated with 331 different spa types; t084 (7.7%), t091 (6.1%) and t012 (71, 5.2%) were predominant. Of 206 participants carrying S. aureus at all three sampling time points, 14.1% carried the same spa type continuously; 5.3% carried different spa types with similar repeat patterns, but 80.6% carried S. aureus with unrelated spa types. MSSA isolates frequently harboured genes encoding enterotoxins (sec: 16.6%, seg: 63.1%, sei: 64.5%) and toxic shock syndrome toxin (tst: 17.5%), but rarely Panton-Valentine leukocidin (lukS-PV/lukF-PV: 0.2%). CONCLUSIONS: MSSA colonizing human nares in the community are clonally highly diverse. Among those constantly carrying S. aureus, clonal lineages changed over time. The proportion of persistent S. aureus carriers was lower than reported elsewhere.

Medical Classification and Terminology Systems in a Secondary Use Context: Challenges and Perils.

Since the introduction of diagnosis-related groups in the German healthcare system, classifying patient diagnosis and procedures with controlled vocabularies have become mandatory and thus creating a large dataset for secondary use in biomedical research. In this paper we present the analysis of an ICD dataset with regards to potentially reimbursement motivated classification and the effects on precision and recall when considering the change history of ICD codes.

Parallel and cross-resistances of clinical yeast isolates determined by susceptibility pattern analysis.

For calculated initial antifungal therapy, knowledge on parallel and cross-resistances are vitally important particularly in the case of multiresistant isolates. Based on a strain collection of 1,062 yeast isolates from a German/Austrian multicentre study, susceptibility pattern analysis (SPA) was used to determine the proportion of parallel and cross-resistances to eight antifungal agents (AFAs) encompassing flucytosine, amphotericin B, azoles (fluconazole, voriconazole and posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin). A total of 414 (39.0%) isolates were resistant for one or more of the AFAs. Resistance to one AFA was shown for 18.1% of all isolates. For 222 isolates (20.9%), resistance to two to seven AFAs was noted (7.7%; 7.7%; 3.6%; 1.0%; 0.7% and 0.2% to 2, 3, 4, 5, 6 and 7 antifungal compounds, respectively). Partial parallel resistances within the azole and echinocandin classes, respectively, were found for 81 (7.6%) and 70 (6.6%) isolates. Complete parallel resistances for azoles, echinocandins and combined for both classes were exhibited by 93 (8.8%), 18 (1.7%) and 6 (0.6%) isolates, respectively. Isolates displaying cross-resistances between azoles and echinocandins were infrequently found. Highly resistant isolates (resistance to ≥6 AFAs) were almost exclusively represented by Candida albicans. Highly standardized testing of AFAs in parallel and from the same inocula followed by SPA allows detailed insights in the prevalence and distribution of susceptibility patterns of microbial isolates.

Longitudinal data driven study design.

In this paper we present a method for processing EHR data into a longitudinal data model and examples for using this model to identify patients cross-sectionally and longitudinally as well as testing study designs retrospectively. Our data model describes measurements on four dimensions: the associated patient, observed feature, data source and time of survey. The transformation of structured source data into our model is defined by rules written in XML. To showcase the flexibility of the proposed longitudinal data model, we present an evolution of a retrospective study design as well as an example for interpreting biomarkers in emergency situations. With the proposed longitudinal data model complex queries can be performed, study designs tested and optimized.

Development, implementation, and evaluation of a structured reporting web tool for abdominal aortic aneurysms.

BACKGROUND: The majority of radiological reports are lacking a standard structure. Even within a specialized area of radiology, each report has its individual structure with regards to details and order, often containing too much of non-relevant information the referring physician is not interested in. For gathering relevant clinical key parameters in an efficient way or to support long-term therapy monitoring, structured reporting might be advantageous. OBJECTIVE: Despite of new technologies in medical information systems, medical reporting is still not dynamic. To improve the quality of communication in radiology reports, a new structured reporting system was developed for abdominal aortic aneurysms (AAA), intended to enhance professional communication by providing the pertinent clinical information in a predefined standard. METHODS: Actual state analysis was performed within the departments of radiology and vascular surgery by developing a Technology Acceptance Model. The SWOT (strengths, weaknesses, opportunities, and threats) analysis focused on optimization of the radiology reporting of patients with AAA. Definition of clinical parameters was achieved by interviewing experienced clinicians in radiology and vascular surgery. For evaluation, a focus group (4 radiologists) looked at the reports of 16 patients. The usability and reliability of the method was validated in a real-world test environment in the field of radiology. RESULTS: A Web-based application for radiological "structured reporting" (SR) was successfully standardized for AAA. Its organization comprises three main categories: characteristics of pathology and adjacent anatomy, measurements, and additional findings. Using different graphical widgets (eg, drop-down menus) in each category facilitate predefined data entries. Measurement parameters shown in a diagram can be defined for clinical monitoring and be adducted for quick adjudications. Figures for optional use to guide and standardize the reporting are embedded. Analysis of variance shows decreased average time required with SR to obtain a radiological report compared to free-text reporting (P=.0001). Questionnaire responses confirm a high acceptance rate by the user. CONCLUSIONS: The new SR system may support efficient radiological reporting for initial diagnosis and follow-up for AAA. Perceived advantages of our SR platform are ease of use, which may lead to more accurate decision support. The new system is open to communicate not only with clinical partners but also with Radiology Information and Hospital Information Systems.