[Digital health applications (DiGA) in the area of tension between progress and criticism : Discussion paper from the "Digital health" specialist group of the German Informatics Society]. / Digitale Gesundheitsanwendungen (DiGA) im Spannungsfeld von Fortschritt und Kritik : Diskussionsbeitrag der Fachgruppe "Digital Health" der Gesellschaft für Informatik e. V.

Since December 2019, digital health applications (DiGA) have been included in standard care in Germany and are therefore reimbursed by the statutory health insurance funds to support patients in the treatment of diseases or impairments. There are 48 registered DiGA listed in the directory of the Federal Institute of Drugs and Medical Devices (BfArM), mainly in the areas of mental health; hormones and metabolism; and muscles, bones, and joints. In this article, the "Digital Health" specialist group of the German Informatics Society describes the current developments around DiGA as well as the current sentiment on topics such as user-centricity, patient and practitioner acceptance, and innovation potential. In summary, over the past three years, DiGA have experienced a positive development, characterized by a gradually increasing availability of various DiGA and coverage areas as well as prescription numbers. Nevertheless, significant regulatory adjustments are still required in some areas to establish DiGA as a well-established instrument in long-term routine healthcare. Key challenges include user-centeredness and the sustainable use of the applications.

Current Status and Future Directions: The Application of Artificial Intelligence/Machine Learning for Precision Medicine.

Technological innovations, such as artificial intelligence (AI) and machine learning (ML), have the potential to expedite the goal of precision medicine, especially when combined with increased capacity for voluminous data from multiple sources and expanded therapeutic modalities; however, they also present several challenges. In this communication, we first discuss the goals of precision medicine, and contextualize the use of AI in precision medicine by showcasing innovative applications (e.g., prediction of tumor growth and overall survival, biomarker identification using biomedical images, and identification of patient population for clinical practice) which were presented during the February 2023 virtual public workshop entitled "Application of Artificial Intelligence and Machine Learning for Precision Medicine," hosted by the US Food and Drug Administration (FDA) and University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI). Next, we put forward challenges brought about by the multidisciplinary nature of AI, particularly highlighting the need for AI to be trustworthy. To address such challenges, we subsequently note practical approaches, viz., differential privacy, synthetic data generation, and federated learning. The proposed strategies - some of which are highlighted presentations from the workshop - are for the protection of personal information and intellectual property. In addition, methods such as the risk-based management approach and the need for an agile regulatory ecosystem are discussed. Finally, we lay out a call for action that includes sharing of data and algorithms, development of regulatory guidance documents, and pooling of expertise from a broad-spectrum of stakeholders to enhance the application of AI in precision medicine.

An overview and a roadmap for artificial intelligence in hematology and oncology.

BACKGROUND: Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many medical professionals and researchers, it often remains unclear what AI can and cannot do, and what are promising areas for a sensible application of AI in hematology and oncology. Finally, the limits and perils of using AI in oncology are not obvious to many healthcare professionals. METHODS: In this article, we provide an expert-based consensus statement by the joint Working Group on "Artificial Intelligence in Hematology and Oncology" by the German Society of Hematology and Oncology (DGHO), the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), and the Special Interest Group Digital Health of the German Informatics Society (GI). We provide a conceptual framework for AI in hematology and oncology. RESULTS: First, we propose a technological definition, which we deliberately set in a narrow frame to mainly include the technical developments of the last ten years. Second, we present a taxonomy of clinically relevant AI systems, structured according to the type of clinical data they are used to analyze. Third, we show an overview of potential applications, including clinical, research, and educational environments with a focus on hematology and oncology. CONCLUSION: Thus, this article provides a point of reference for hematologists and oncologists, and at the same time sets forth a framework for the further development and clinical deployment of AI in hematology and oncology in the future.

Digitalization and disruptive change in rheumatology.

INTRODUCTION: Recently, many sectors have seen disruptive changes due to the rapid progress in information and communication technology (ICT). The aim of this systematic literature review was to develop a first understanding of what is known about new ICTs in rheumatology and their disruptive potential. METHODS: PubMed, LIVIVO, and EBSCO Discovery Service (EDS) databases were searched for relevant literature. Use of new ICTs was identified, categorized, and disruptive potential was discussed. Articles from 2008 to 2021 in German and English were considered. RESULTS: A total of 3539 articles were identified. After application of inclusion/exclusion criteria, 55 articles were included in the analyses. The majority of articles (48) used a non-experimental design or detailed expert opinion. The new ICTs mentioned in these articles could be allocated to four main categories: technologies that prepare for the development of new knowledge by data collection (n = 32); technologies that develop new knowledge by evaluation of data (e.g., by inventing better treatment; n = 11); technologies that improve communication of existing knowledge (n = 32); and technologies that improve the care process (n = 29). Further assessment classified the ICTs into different functional subcategories. Based on these categories it is possible to estimate the disruptive potential of new ICTs. CONCLUSION: ICTs are becoming increasingly important in rheumatology and may impact patients' lives and professional conduct. The properties and disruptive potential of technologies identified in the articles differ widely. When looking into ICTs, doctors have focused on new diagnostic and therapeutic procedures but rarely on their disruptive potential. We recommend putting more effort into investigation of whether ICTs change the way rheumatology is performed and who is in control of it. Especially technologies that potentially replace physicians with machines, take control over the definition of quality in medicine, and/or create proprietary knowledge that is not accessible for doctors need more research.

Pregabalin improves axon regeneration and motor outcome in a rodent stroke model.

Ischaemic stroke remains a leading cause of death and disability worldwide. Surviving neurons in the peri-infarct area are able to establish novel axonal projections to juxtalesional regions, but this regeneration is curtailed by a growth-inhibitory environment induced by cells such as reactive astrocytes in the glial scar. Here, we found that the astroglial synaptogenic cue thrombospondin-1 is upregulated in the peri-infarct area, and hence tested the effects of the anticonvulsant pregabalin, a blocker of the neuronal thrombospondin-1 receptor Alpha2delta1/2, in a mouse model of cortical stroke. Studying axonal projections after cortical stroke in mice by three-dimensional imaging of cleared whole-brain preparations, we found that pregabalin, when administered systemically for 5 weeks after stroke, augments novel peri-infarct motor cortex projections and improves skilled forelimb motor function. Thus, the promotion of axon elongation across the glial scar by pregabalin represents a promising target beyond the acute phase after stroke to improve structural and functional recovery.

Reimbursement of innovative pharmaceuticals in English and Spanish hospitals-The example of isavuconazole.

BACKGROUND: Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck-based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge-based healthcare systems. OBJECTIVES: The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain. PATIENTS/METHODS: Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied. RESULTS: This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay. CONCLUSIONS: Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs' cost-effectiveness and assessing its added value into reimbursement decisions is highly relevant.

Principal-agent theory-based cost and reimbursement structures of isavuconazole treatment in German hospitals.

BACKGROUND: Isavuconazole (ISA) is a frequently used antifungal agent for the treatment of invasive fungal diseases (IFDs). However, hospital reimbursement data for ISA is limited. OBJECTIVES: The primary objective of this study was to analyse the different perspectives of relevant stakeholders and the (dis)incentives for the administration of ISA in Germany. To that aim, the health economic effects of using ISA from a hospital management perspective were analysed. PATIENTS/METHODS: Based on principal-agent theory (PAT), the perspectives of (a) the patient (principal) as well as (b) physicians, (c) pharmacists and iv. hospital managers (all agents) were analysed. For the evaluation of the cost-containment and reimbursement strategies of ISA, the German diagnosis-related group (G-DRG) system was used. RESULTS: Hospitals individually negotiating additional payments for innovative treatment procedures (zusatzentgelte [ZE]) within the G-DRG system is a key element of hospital management for the reduction of total healthcare expenditure. Our analysis demonstrated the beneficial role of ISA in healthcare resource utilisation, primarily due to a shortened overall length of hospital stay. Depending on underlying disease, coded G-DRG and ISA formulation, large differences in total reimbursement and the amount of ZE was shown. The PAT demonstrated disincentives for hospital managers to use innovative drugs. CONCLUSIONS: Based on the PAT, beneficial, detrimental and indifferent perspectives of different stakeholders regarding the usage of ISA were shown. A reduction of bureaucratic hurdles is needed in Germany for the extension of effective and innovative antifungal treatment strategies with ISA.

Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.

Stroke leads to the degeneration of short-range and long-range axonal connections emanating from peri-infarct tissue, but it also induces novel axonal projections. However, this regeneration is hampered by growth-inhibitory properties of peri-infarct tissue and fibrotic scarring. Here, we tested the effects of epothilone B and epothilone D, FDA-approved microtubule-stabilizing drugs that are powerful modulators of axonal growth and scar formation, on neuroplasticity and motor outcomes in a photothrombotic mouse model of cortical stroke. We find that both drugs, when administered systemically 1 and 15 days after stroke, augment novel peri-infarct projections connecting the peri-infarct motor cortex with neighboring areas. Both drugs also increase the magnitude of long-range motor projections into the brainstem and reduce peri-infarct fibrotic scarring. Finally, epothilone treatment induces an improvement in skilled forelimb motor function. Thus, pharmacological microtubule stabilization represents a promising target for therapeutic intervention with a wide time window to ameliorate structural and functional sequelae after stroke.

Health Applications for Corporate Health Management.

INTRODUCTION: Many corporate organizations around the world are looking at new ways to improve the health and well-being of their employees. Many have begun to use m-health approaches and unique applications (apps) to provide assistance. In Germany, both m-health and occupational health management (OHM) are growing quickly. Therefore, we hypothesized that the combination-apps usage in OHM-is growing as well. We studied the usage of health apps in large corporations for health management of employed individuals. METHODS: To understand the environment in Germany, a two-part study was conducted. First, an extensive literature search was done and second, interviews were conducted with 12 of the 20 biggest companies' health management representatives. RESULTS: Using key search terms, 5,445 peer-reviewed journal articles traced with German databases and on PubMed were reviewed. Interestingly and somewhat surprising to the authors, none of them covered our specific topic. Interviews were conducted with 60% of the companies indicated. Only 3 out of 12 companies use apps. Four companies are piloting apps. With one exception, apps cover well-known areas such as food coaching, physical motion, smoking cessation, stress prevention, and other health-related subjects. One app used sensors in work clothing to prevent unhealthy motion. With a few exceptions, there has been no evaluation of the utility and utilization of apps. DISCUSSION: Current app usage in corporate health management in Germany is surprisingly low. Apps need to be better evaluated. Main obstacles-which could be resolved in the future-are legal restrictions (especially on data security), the lack of company-owned smart phones, misfit of apps and corporate health strategy, a lack of app evaluation, and high app prices.

Use of antidiabetic agents in the treatment of gestational diabetes mellitus in Germany, 2008-2012.

AIM: Adequate blood glucose control during pregnancy is important because gestational diabetes mellitus (GDM) is known to have adverse effects on the mother and child. Due to an increasing prevalence of GDM in recent years, more information on the use of different antidiabetic agents is required, which was the aim of the present study. MATERIAL AND METHODS: Data from 32 diabetic practices in Germany were collected from January 2008 to December 2012 and analyzed using the Disease Analyzer Database. All women with International Classification of Diseases diagnosis O24 (that is, GDM) participated, except for patients with known type I or II diabetes mellitus, who were excluded. Analysis focused on the proportion of women requiring drug treatment in general. Thereafter, subanalysis was performed with a focus on the administration of different antidiabetic agents, namely insulin, metformin, and sulfonylurea. RESULTS: Within the given timeframe, medication-based treatment for GDM significantly rose to reach 30.8% of all women with GDM. Both the administration of insulin and metformin grew considerably within the 5-year period with metformin being increasingly used without supplemental insulin and at lower dosages. Within the insulin treatment arm, insulin analogues became increasingly important. The proportion of sulfonylurea remained stable (0.2%). CONCLUSIONS: GDM is more often treated with antidiabetic agents and, due to the fact that metformin is more frequently prescribed, it can be assumed that it is increasingly regarded as a safe and effective alternative to insulin.

Failure to address potential bias in non-randomised controlled clinical trials may cause lack of evidence on patient-reported outcomes: a method study.

OBJECTIVES: We conducted a workup of a previously published systematic review and aimed to analyse why most of the identified non-randomised controlled clinical trials with patient-reported outcomes did not match a set of basic quality criteria. SETTING: There were no limits on the level of care and the geographical location. PARTICIPANTS: The review evaluated permanent interstitial low-dose rate brachytherapy in patients with localised prostate cancer and compared that intervention with alternative procedures such as external beam radiotherapy, radical prostatectomy and no primary therapy. PRIMARY OUTCOME MEASURE: Fulfilment of basic inclusion criteria according to a Participants, Interventions, Comparisons, Outcomes (PICO) framework and accomplishment of requirements to contain superimposed risk of bias. RESULTS: We found that 21 of 50 excluded non-randomised controlled trials did not meet the PICO inclusion criteria. The remaining 29 studies showed a lack in the quality of reporting. The resulting flaws included attrition bias due to loss of follow-up, lack of reporting baseline data, potential confounding due to unadjusted data and lack of statistical comparison between groups. CONCLUSIONS: With respect to the reporting of patient-reported outcomes, active efforts are required to improve the quality of reporting in non-randomised controlled trials concerning permanent interstitial low-dose rate brachytherapy in patients with localised prostate cancer.

[Sickness funds' activities for early detection, prevention and health promotion in depressive disorders]. / Krankenkassenprogramme zur Früherkennung, Prävention und Gesundheitsförderung bei Depressionen.

OBJECTIVE: We analyzed programs managed by the ten biggest social health insurance companies in Germany that aim at early detection, prevention, and promotion of health in depression. METHODS: We conducted interviews with the responsible managers and studied relevant web sites. RESULTS: The content of these programs ranges from internet-based offers to relaxation techniques. There is very little information publicly available on the results of these programs; the same holds true for the number of participants, efficiency, and cooperation with physicians. CONCLUSION: There is a strong need to investigate results and efficiency of the programs.

A clinician's perspective on pharmacoeconomics and rheumatology.

This paper provides a brief introduction into pharmacoeconomics and its role in rheumatology from the perspective of a clinician, and is regarded as providing complementary simplified explanations for rheumatologists, which are used in a in much greater sophistication and complexity in other articles in this supplement. Different definitions of pharmacoeconomics are discussed. In the major part of the article, typical pharmacoeconomic methods are explained and illustrated using examples derived from rheumatology: cost, cost-benefit analysis, cost-effectiveness analysis, cost-utility analysis, decision tree analysis, and Markov models. These methods are discussed in terms of strengths and weaknesses and their implications for medical practice.

[Communication of psychiatric hospitals' specialization]. / Kommunikation von Behandlungsschwerpunkten psychiatrischer Kliniken.

OBJECTIVE: To analyze whether specialization of psychiatric hospitals results in quality improvement, and whether it can and should be measured and communicated to patients and ambulatory care physicians. METHODS: Depth interviews with key deciders in the German psychiatric care system. RESULTS: There are several specializations within the system of psychiatric hospital care which can be communicated to patients and physicians; this would facilitate choice of hospital. There is no national database available yet. CONCLUSIONS: Data collection and communication as provided by an independent organization would improve knowledge about hospital specialization.

Long-term future of telemedicine in Germany: the patient's, physician's, and payer's perspective.

While the near-term future of telemedicine development in Germany is quite clear, the long-term future has not been investigated. To determine telemedicine's long-term future in Germany, in-depth interviews were conducted with 20 key decision-makers in the German healthcare system. Interviewees included payers, doctors and their professional associations; and patients and their organizations. These individuals were asked what their expectations were in the application of telemedicine. According to the interviewees, several changes in the healthcare system as a whole will occur, which influence telemedicine. These include increase in cost pressure; the changing role of the payers and companies--as opposed to public organizations--playing a more active role in managing care. Physicians foresee more changes than payers do. Patients expect telemedicine to strengthen their role as patients. Most important telemedicine applications will be the "Gesundheitskarte" (a smart card enabling access to patient records), telemedicine as an enabling technology for other provider integration models, information systems for patients, and telemonitoring. The future looks promising for telemedicine in Germany.