Abstract Background Chronic conditions cause millions of deaths annually worldwide. Remote patient monitoring using wearable devices and sensors, combined with machine learning (ML), offers promising strategies for disease management. However, diverse methodological approaches and study designs impede comparability and the development of best practice guidelines. Methods A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Four scientific databases were searched for relevant prospective studies published between 2014 and 2024. Studies had to use ML to predict disease outcomes of chronic conditions in remotely monitored patients. The studies were tagged for characteristics such as health outcomes, dataset, monitored parameters, and algorithms. Results From 6668 initially identified studies, 76 met inclusion criteria. 73.7% of studies were considered to have a high risk of bias, mainly due to methodological shortcomings in the Analysis domain. Parkinson’s disease was most frequently monitored, followed by diabetes and chronic obstructive pulmonary disease (COPD). Wearable devices were the predominant remote sensors, with accelerometer data being the most common parameter. Tree-based algorithms were most frequent, and studies using leave-one-out cross-validation showed significantly higher accuracy. Feature engineering and publication year were also significantly associated with model performance. Conclusion This review highlights both progress and challenges in applying ML to chronic disease monitoring. While conditions like Parkinson’s, COPD, and diabetes are well-represented, others such as liver and kidney diseases are underexplored. Future research should prioritize standardization of methodologies, model interpretability, and ethical considerations including data privacy and algorithmic fairness. When properly implemented, ML-driven remote monitoring has the potential to enhance patient care, reduce complications, and deepen our understanding of chronic conditions. However, addressing challenges in reproducibility, generalizability, and clinical integration is crucial for advancing the field.

Background The integration of digitalisation, including artificial intelligence (AI), is becoming increasingly important in healthcare. It is transforming areas such as diagnostics, therapeutic planning and patient monitoring. However, research indicates that many medical students and physicians feel unprepared to use these technologies in their daily practice. This study provides insights into the opportunities and challenges of integrating digitalisation and AI into medical curricula with a focus on general medicine curricula in German-speaking European countries.Objective The objectives are to assess the perceived importance of digital and AI topics in medical education, evaluate the status of their integration into general medicine curricula and identify the challenges of their implementation.Design A sequential mixed-methods approach was used. First, a qualitative analysis of documents from university websites was conducted. Subsequently, 59 general medicine departments in Austria, Germany and Switzerland were invited to participate in a quantitative anonymous online survey. Descriptive statistics were analysed using SPSS 30.0.Results The survey was completed by half of Austrian universities and more than one-third of the German universities. None of the Swiss universities responded, resulting in a total response rate of 28.3%. The results reveal discrepancies between perceived importance and actual implementation, indicating a clear need for more courses on digitalisation and AI in medicine for medical students. Identified challenges with impact on limited implementation (especially of AI-related topics) were curriculum overload, a lack of qualified lecturers, lack of materials and a lack of resources.Conclusions General medicine is the largest segment of healthcare services in Austria and Germany. Respondents highlighted a strong demand for digitalisation and AI to be integrated into general medicine curricula, which is consistent with other studies and the current literature. Our results underscore the urgent need for the systematic inclusion of competencies regarding digital tools and AI to adequately prepare future physicians for real-world challenges.

Background: The supply of pharmaceuticals is undergoing structural change due to internet mail orders, a shortage of skilled workers, and the decreasing density of community pharmacies. Since January 1, 2024, Germany also has an electronic prescription procedure, the e-prescription. This study aims to answer the question how digitalization has changed access to pharmaceuticals. Methods: Semi-structured expert interviews were conducted between September 2023 and March 2024. Relevant experts were identified and surveyed about their experience with the influence of digitalization that has so far been observed, about its practicality, and their expectations and outlook regarding the consequences for the supply of medicines. Therefore, only experts from self-governing bodies, the Gematik GmbH, payers, and patient representatives were selected. The interviews were recorded and transcribed. The transcripts were analyzed using MAXQDA. Results: A total of 9 interviews were conducted. Regarding the effects of digitalization on patient care provided by community and mail order pharmacies, the experts overall regarded mail order pharmacies as high-performance companies that comply with the safety principles required in the pharmaceutical trade. All experts could see the mail order trade's impact on the density of community pharmacies. The shortage of skilled workers was confirmed by all experts, and digitalization can help mitigate this problem. However, an excessive expansion of mail order companies can disadvantage patients. Concerning e-prescriptions, the expert interviews revealed that e-prescriptions and the telematics infrastructure (TI) are still experiencing difficulties. Despite the costs, the experts surveyed believe that improvements in patient care and patient safety will enhance patient rights. Discussion: Digitization has a beneficial effect by increasing access to pharmaceutical care. People can access medicines more easily through mail orders and e-prescriptions depending on how they are dispensed. However, some groups of people do not benefit from the new advantages, resulting in the need to further reduce this imbalance in the future. The preservation of community pharmacies for the purpose of individual advice and emergency pharmacy services is another challenge that we have to face as a result of digitalization. Conclusion: The e-prescription still has its shortcomings and is currently testing the patience of doctors, pharmacists, and prescription recipients. If stable, it will improve both patient care and patient safety. Future studies will need to demonstrate that the access-to-medicines gap can be filled and technical difficulties further reduced.

Chronic pain represents the defining and quality-of-life limiting feature in patients with cancer pain (CP) or chronic non-cancer pain (CNCP) and is often treated with opioids. Over time, opioid use is frequently accompanied by necessity of an increasing dose due to pharmacological tolerance and progress of the underlying diseases. The potential side effects were found to correlate with accelerating doses. More recently, the opioid crisis in the United States has drawn attention to the adverse effects and toxicities. Until today it is unclear what high-dose opioid therapy is and guidelines are inconsistent regarding an evidence-based threshold. This systematic review and meta-analysis aim to determine a threshold for high-dose opioid therapy. A systematic literature search was conducted in 4 databases from earliest publication available until May 2025. Studies were eligible if participants with CP or CNCP were able to self-titrate their opioid dosage to reach a sufficient pain relief. 4305 records were screened. Nineteen included studies with a total of 3111 participants investigating eight different opioids were included. The studies were assessed for risk of bias. Results were synthesised as oral morphine equivalents (OMEs). The meta-analysis found a weighted mean of 74.7 mg OME per day and the 97.5

Objectives:This exploratory study aimed to examine the somatosensory profiles of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and systemic sclerosis (SSc) using quantitative sensory testing (QST). We sought to identify distinct patterns of sensory alterations to enhance the understanding of pain mechanisms in these conditions and to generate hypotheses for future mechanistic research and therapy approaches. Methods:Patients with RA, PsA, axSpA, and SSc underwent QST on both hands to evaluate all somatosensory submodalities. Standardised assessment, following the German Research Network on Neuropathic Pain protocol, included mechanical detection threshold (MDT) and vibration detection threshold (VDT) as well as thermal detection and pain thresholds. Results:We enrolled 80 patients (20 with RA, PsA, axSpA, SSc) and 20 controls. Significant differences in MDT (RA: β = 0.90, P =.025; PsA: β = 1.30, P =.001; axSpA: β = 0.80, P =.045; SSc: β = 0.86, P =.030) and VDT (RA: β = -0.33, P =.003; PsA: β = -0.23, P =.033; axSpA: β = -0.30, P =.006; SSc: β = -0.17, P =.126) were observed compared with controls. All disease groups exhibited pathological allodynia (RA: 15%, PsA: 25%, axSpA: 15%, SSc: 5%, and controls: 0%), with sensory processing alterations occurring independently of inflamed areas. No association was found between QST-detected sensory alterations and disease activity, duration, or inflammatory markers. Conclusions:Patients with RA, PsA, axSpA, and SSc demonstrate significant alterations in somatosensory processing, including abnormal MDT and VDT, and pathological allodynia that appear independent of inflamed areas. These sensory changes do not correlate with disease activity, duration, inflammatory markers, or therapeutic approach, indicating that they may result from mechanisms distinct from inflammation.

Background Funded by the Federal Ministry of Health, the Federal Institute for Drugs and Medical Devices, in cooperation with the Federal Statistical Office, developed an electronic death certificate app and tested it in two federal states to assess its user-friendliness and acceptance. Death certificates are filled out by hand and pass through various offices for transcription and coding before cause of death statistics are published. The certificates are often incorrect and difficult to read. In Germany, there are 16 different forms depending on the federal state, and none of them meet World Health Organization (WHO) requirements for international comparability. MethodsA mixed-methods approach was used with validated questionnaires and semi-structured guided interviews (February to September 2023). The quantitative data were analysed descriptively with SPSS and the qualitative data were analysed using content analysis with MAXQDA. ResultsIn two federal states, a total of 89 out of 201 physicians completed the surveys and a further 11 were interviewed. Almost all respondents (n = 70) have a positive attitude towards digitalisation in healthcare (94%), see a benefit in processes and organisation (93%) and have no concerns about data security (73%). The majority confirmed the user-friendliness of the eTB app. The qualitative data highlighted that plausibility checking, error prevention and improved readability were convincing arguments in favour of the eTB app. ConclusionThe eTB app is easy to use and useful. In particular, the fast data transfer makes the eTB app an important milestone in digitalization. Improvements are required for use in practice.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

CONTEXT:Palliative care aims to improve the quality of life in patients with progressive diseases such as cancer. Effective cancer pain management is a major challenge of palliative treatment. Empirical data on the prevalence of cancer pain, the efficiency of pain treatment and influencing factors are scarce. OBJECTIVES:Here, we investigated pain in cancer patients treated on inpatient palliative care wards in Germany. METHODS:N = 4779 data sets provided by the German Palliative Care Registry from yearly evaluation periods between 2015 and 2020 were included. Pain ratings were assessed by professionals through a checklist of symptoms and problems (HOPE-SP-CL). RESULTS:More than half of the included patients suffered from moderate/severe pain at the beginning of inpatient palliative care and in 71% of these patients, pain relief was achieved at the end of inpatient treatment. Pain intensity, depression and ECOG performance status at admission were weak predictors of later pain relief. The highest pain intensity at the beginning and least pain relief were found in patients with bone and cartilage cancer. The highest percentage of adequate pain control (81%) was seen in 2020. CONCLUSION:Data from the German Palliative Care Registry confirmed that although increasingly better addressed over the years, insufficiently controlled cancer pain remains a challenge for palliative care units. Patient-specific (e.g. psychological comorbidity) and cancer-related (e.g. bone or cartilage cancer) risk factors for poor pain treatment underline the need for individualized multimodal pain management including psychological support.

Seltene Erkrankungen werden oft erst spät erkannt. Ihre Diagnose ist aufgrund der Diversität, Komplexität und Heterogenität klinischer Symptome besonders anspruchsvoll. Computergestützte diagnostische Hilfen, oft als „diagnostic decision support systems“ (DDSS) bezeichnet, sind vielversprechende Tools, um die Zeit bis zur Diagnose zu verkürzen. DDSS sind trotz erster positiver Evaluationen noch nicht sehr weit verbreitet, was unter anderem auf die mangelnde Integration in existierende klinische oder Praxisinformationssysteme zurückgeführt werden kann. Dieser Beitrag bietet einen Einblick in aktuell existierende DDSS, die ohne Zugriff auf elektronische Patientenakten funktionieren und nur einfach zu beschaffende Informationen benötigen. Im Rahmen einer systematischen Literaturrecherche wurden 8 Beiträge identifiziert, in denen DDSS untersucht werden, die bei der Diagnose seltener Erkrankungen unterstützen können und dabei keinen Zugriff auf elektronische Patientenakten oder andere Informationssysteme in Praxen und Kliniken verlangen. Die wichtigsten Vor- und Nachteile der identifizierten Systeme zur Unterstützung bei der Diagnostik seltener Erkrankungen wurden extrahiert und zusammenfassend dargestellt. Symptom-Checker sowie DDSS auf Basis von Porträtfotos und Schmerzzeichnungen existieren bereits. Der Reifegrad dieser Anwendungen ist unterschiedlich. DDSS stehen aktuell noch vor einigen Herausforderungen – so gibt es Bedenken zu Datenschutz und Genauigkeit, zudem sind die Akzeptanz und Bekanntheit noch eher gering. Dem gegenüber steht ein großes Potenzial für eine schnellere Diagnosestellung, insbesondere bei seltenen Erkrankungen, die aufgrund ihrer großen Anzahl und geringen Bekanntheit leicht übersehen werden. Der Einsatz von DDSS sollte daher von Ärztinnen und Ärzten im Einzelfall gut abgewogen werden.

Zusammenfassung Hintergrund Diagnose und Therapie neuropathischer Schmerzen stellen Behandler:innen vor Herausforderungen, insbesondere wenn eine elektroneurographisch nicht nachweisbare Kleinfaserneuropathie (Small-fiber-Neuropathie [SFN]) vorliegt. Fragestellung Diese Arbeit sensibilisiert für seltene, teilweise behandelbare Ursachen neuropathischer Schmerzen im Kontext einer nicht leicht zu diagnostizierenden SFN. Wir unterstreichen die Bedeutung von Anamnese und körperlicher Untersuchung. Autonome Symptome sind häufig mit SFN assoziiert, oft bestehen vielfältige Beschwerden. Material und Methoden Selektive Literaturrecherche zur Darstellung wichtiger Symptome der SFN sowie differenzialdiagnostischer und therapeutischer Schritte im Kontext seltener Erkrankungen mit Fokus auf das autonome Nervensystem Ergebnisse Neuropathische Schmerzen schränken die Lebensqualität deutlich ein. Um die Zeit bis zur Diagnose und Therapie zu verkürzen, empfehlen wir eine strukturierte Anamnese mit Erfassung sensibler Plus- und Minussymptome, eine körperliche Untersuchung und die Erfassung vegetativer Zeichen. Ist die erste Ursachensuche nicht erfolgreich, sollten seltene Ursachen wie die behandelbare Transthyretin(ATTR)-Amyloidose, ein Morbus Fabry oder Autoimmunerkrankungen in Betracht gezogen werden, insbesondere bei fortschreitenden und/oder begleitenden autonomen Symptomen. Schlussfolgerung Die Diagnostik und Therapie seltener Ursachen von SFN bedarf oft einer interdisziplinären Zusammenarbeit und gegebenenfalls einer Überweisung an spezialisierte Zentren, um Betroffene bestmöglich versorgen zu können.

The clinical picture of people with Ehlers–Danlos syndromes (EDS) is complex and involves a variety of potential causes of pain. This poses major challenges to patients and healthcare professionals alike in terms of diagnosis and management of the condition. The aim of the article was to provide an overview of the specific pain management needs of patients with EDS and address their background. A selective literature search was performed to highlight the current state of research on pain management in EDS patients. Affected patients require multimodal pain management considering their individual needs, disease-specific features, and comorbidities. Medical awareness and evidence need to be further improved to enhance the medical care situation of these patients with complex needs.

Background In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. Methods An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. Results 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. Conclusions This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

Background: Neuropathic pain is difficult to diagnose and treat. Small fiber neuropathy (SFN) flies under the radar of nerve conduction studies.Objectives: The importance of a structured patient history and physical examination in the context of neuropathic pain is emphasized. Describing SFN as an important cause, the authors consider rare but partially treatable differential diagnoses. They conclude that autonomic symptoms are frequently associated, often presenting with diverse symptoms.Methods: A selective literature research to present SFN symptoms as well as differential diagnostic and therapeutic steps in the context of SFN and rare diseases focusing on the autonomic nervous system.Results: Neuropathic pain significantly reduces quality of life. To shorten the time until diagnosis and to initiate therapy, the authors recommend a structured patient history including sensory plus and minus symptoms and non-specific autonomic signs. If the initial search for the cause is not successful, rare causes such as treatable transthyretin (ATTR) amyloidosis and Fabry's disease or autoimmune causes should be considered, particularly in the case of progressive and/or autonomic symptoms.Conclusion: The diagnosis and therapy of rare SFN requires interdisciplinary collaboration and, in many cases, a referral to specialized centers to achieve the best patient care.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motoneuron. It is associated with a life expectancy of 2-4 years after diagnosis. Individuals experience paralysis, dysphagia, respiratory failure and loss of communicative function, rendering advance care planning (ACP) critically important. This systematic review primarily aimed to internationally compare the application of advance directives (AD) and ACP in ALS. Its secondary aim was to identify ACP preferences, identify fields for future research and to generate recommendations for improving patient care through ACP.MethodsWe conducted a systematic literature review and meta-analysis. Five electronic databases (Embase, Medline, Scopus, PsycInfo and CENTRAL) were searched for qualitative and quantitative primary literature from 1999 to 2024. Cross-references were used to identify additional publications. Study selection was performed based on inclusion criteria. Number and content of AD were extracted systematically. After statistical analysis consecutive meta-analysis was performed for international differences and changes over time. Quality assessment of studies was performed using the MMAT (Mixed Methods Appraisal Tool). PROSPERO Registration (June 07, 2021) : CRD42021248040.ResultsA total of 998 records was screened of which 26 were included in the synthesis. An increase in publication numbers of 88.9% was observed from 1999 to 2024. Results regarding use and content of AD were heterogeneous and international differences were detected. AD were signed in 60.4% of records (1,629 / 2,696 patients). The number of AD decreased over time when separating the review period in two decades (1st 1999-2011: 78% vs. 2nd 2012-2024: 42%). Study quality was superior in qualitative and mixed method designs compared to quantitative studies.ConclusionFurther prospective studies should include detailed analyses on preferences regarding ventilation and artificial nutrition in ALS and should encompass countries of the global south. Despite the complexity of ACP with regard to individual patient needs, ACP should be part of each individual support plan for ALS patients and should specifically comprise a discussion on the preferred place of death. The available disease-specific AD documents should be preferred.