BACKGROUND:The establishment of the complementary infrastructures Medical Informatics Initiative (MII) and the Network of University Medicine (NUM) has significantly advanced the medical research landscape in Germany. Both infrastructures focus on the cross-institutional integration of health data as the basis for strengthening medical research, with the MII focusing on the standardization and integration of routine university clinical data and the NUM representing a central infrastructure for clinical studies and data sharing. Within the project 'NUM Routine Data Platform' (NUM-RDP), a federated record linkage approach was implemented across 34 affiliated German university hospitals. Accordingly, a federated Trusted Third Party (fTTP) performed pseudonymization and privacy-preserving record linkage across all the participating sites. This work aims to extend the established fTTP approach to managing consent and withdrawal while considering the current legal frameworks and research initiatives for the use of health data. METHODS:A concept for an extended fTTP, termed 'fTTP Consent', is proposed to bridge communication gaps between different sites, facilities and components. This allows for central coordination for the implementation of patients' consent decisions regarding the storage, transfer and scientific use of their health data in a uniform manner. RESULTS:Two practical use cases for an 'fTTP Consent' have been identified and conceptualized. First, the cross-site improvement of workflows and automated processes should be performed to ensure that consent data are correct in formal, legal, semantic and syntactic terms. Second, the cross-site improvement of automated notification processes for new or updated consent data, including respective withdrawal- and objection-processes, should be performed. CONCLUSIONS:In this study, the 'fTTP Consent' has been proposed to reduce communicatory and personnel efforts. The correct and up-to-date realization of data subject rights should be ensured using the NUM-RDP as an example. The designed concept could help to overcome challenges in different consent scenarios (opt-in, opt-out). Furthermore, it could streamline communication and data linkage processes between institutions and countries in future research projects.

BACKGROUND:Medical registries are essential instruments for evidence-based healthcare, providing real-world data that support research, quality assurance, and health policy. Despite their growing relevance, an overview of existing registries in Germany is lacking. OBJECTIVE:This study aims to map the current landscape of medical registries in Germany and to describe their characteristics, funding structures, and potential for future interoperability between registries and real-world data. METHODS:Data from the national online registry catalogue, which is developed in collaboration with the German registry community, are analysed in July 2025. Categorical variables are summarised descriptively, considering only registries that provide information for each item. RESULTS:A total of 423 registries are identified, with founding dates ranging from 1929 to 2025 (median 2013). Only 49% provide information on their legal form, and one third of these have an independent legal status. The funding landscape is highly heterogeneous, with most registries publicly funded, followed by those supported by donations or the pharmaceutical industry. CONCLUSION:Germany hosts a large and diverse registry landscape. Future priorities include improving interoperability, harmonising quality standards, and ensuring sustainable funding to fully realise the potential of curated registry data within the European Health Data Space.

BackgroundLow socioeconomic status is associated with a higher risk for a number of health conditions, including cognitive impairment.ObjectiveWhile the association with economic indicators has been well researched, aim of this paper was to investigate specifically the association between non-economic social deprivation and cognitive functioning later in life.MethodsParticipants without objective cognitive impairment at baseline (n = 91 controls, n = 106 with subjective cognitive decline) of the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) filled out a posthoc survey on social deprivation. Factor analysis identified four non-economic domains of social deprivation (Residential area conditions, Accessibility, Neighborhood support, Household distress). Cognition was assessed via the CERAD neuropsychological battery. Analyses were conducted using linear regression models as well as maximum-likelihood mixed-effects models adjusted for age, gender, years of education, marital status, depression, BMI, heart disease, hypercholesterolemia, hypertension, and diabetes.ResultsAt the time of the survey, cognitive functioning was significantly lower among participants with high deprivation (b = -0.21, p = 0.037). These participants also had a faster rate of cognitive decline (b = -0.07, p = 0.006). Analyses of the deprivation sub-scores revealed statistically significant effects only for Accessibility (b = -0.31, p = 0.001; rate of cognitive decline b = -0.07, p = 0.004).ConclusionsOur findings suggest that non-economic social deprivation, especially in terms of access to a grocery store, pharmacy, postal office, and bus stop, might be relevant for maintaining cognitive functioning in old age. Further research should explore potential mechanisms of how these environmental conditions affect brain aging and neurodegenerative processes.

Abstract Background Pediatric emergencies are rather rare in pre-hospital care. The aim of this study was to analyze the frequency and urgency of pediatric emergency medical service (EMS) missions and to identify age-specific characteristics in EMS utilization in the rural district of Vorpommern-Greifswald in northeastern Germany. Methods In this retrospective observational study, all emergency protocols from ambulance vehicles and emergency physician vehicles from January 1, 2022, to December 31, 2023, in the study region were analyzed using descriptive statistical methods. Patients were categorized into age groups: infants (< 1 year), toddlers (1–5 years), schoolchildren (6–13 years), adolescents (14–17 years), adults (18–64 years), and seniors (≥ 65 years). Results Over the study period, 71,446 patients had an EMS contact, thereof 255 infants (0.4%), 976 toddlers (1.4%), 1,437 schoolchildren (2.0%), 1,395 adolescents (2.0%), 25,220 adults (35.3%), and 42,163 seniors (59.0%). The annual emergency rate among adults ≥ 18 years was nearly three times higher than among minors < 18 years (169 vs. 58 patients per 1,000 inhabitants within the respective age groups). Pediatric cases accounted for 5.7% of all missions. Vehicle dispatches for minors followed a bimodal temporal distribution with peaks between 12:00 and 1:00 p.m. and between 6:00 and 7:00 p.m. Seasonal variation was observed, with the highest dispatch volume in June (10.5% of all pediatric dispatches) and the lowest in February (5.3%). Trauma was more common in minors compared to adults (41.8% vs. 23.1%), with the highest proportion among schoolchildren (52.2%). The proportion of critically ill or injured patients (NACA IV–VII) was lower in minors than in adults (10.2% vs. 20.8%). Physician involvement was more frequent in pediatric missions than in adult missions (39.4% vs. 32.9%). Infants showed the highest physician involvement (53.5%). Conclusions In pediatric missions, the involvement of physicians is high, however, critically ill children are rare. Low exposure to pediatric cases may contribute to insecurity among paramedics and emergency physicians in pediatric emergencies. Therefore, hands-on training in pediatric emergency care is essential. Given the rising demand for EMS, telemedicine could be a valuable addition in rural settings to reduce the burden on physician resources and ensure comprehensive pediatric care. Clinical trial number Not applicable

Background Building on the German national Network Genomic Medicine (nNGM), which has improved access to molecular testing for lung cancer patients, the project DigiNet aims to enhance digital networking via a Network Data Platform (NDP) in order to optimize data exchange and personalized therapy management of non-small cell lung cancer (NSCLC). Methods To analyze facilitating and inhibiting factors from the perspective of healthcare providers (HCPs), qualitative interviews with respect to the implementation process were conducted. Qualitative content analysis in accordance with Kuckartz and Rädiker was undertaken, and the Consolidated Framework for Implementation Research (CFIR) was applied to guide the analysis. Results Overall, 40 HCPs contributed to 51 interviews, with 11 taking part twice. Facilitating factors included the establishment of DigiNet upon the preexisting infrastructure of nNGM and the systematic documentation of treatment data, thereby enabling a comprehensive review of the entire clinical pathway. Especially for peripheral locations, one benefit lies in the improved information flow and networking with nNGM centers. The most frequently reported barrier was the double documentation of patient data, as in-house and the NDP were used in parallel. There is a need for digital interfaces to enable transfer into existing software at each individual clinical site. Conclusions DigiNet highlights the potential of intensified digital networks to optimize precision oncology while underscoring the need to address regulatory and interoperability challenges to ensure integration into routine care.

In Deutschland sind gegenwärtig mindestens 1,8 Millionen von Demenz betroffen; bis 2060 droht ein Anstieg auf 2,1 Millionen Betroffene. Prävention bietet die derzeit beste Möglichkeit zur effektiven Linderung der Krankheitslast. Das Krankheitsrisiko und der Krankheitsverlauf sowie die Effektivität von Präventionsmaßnahmen werden von diversen Faktoren beeinflusst; in Kombination ergeben diese potenziell individuelle Risikoprofile als Grundlage für eine effektive Demenzprävention. Die Hebung dieser Potenziale erfordert kurzfristig insbesondere eine bessere Nutzung bestehender Daten inklusive einer erweiterten Datenerfassung und Nutzbarmachung für die Forschung, wodurch bevölkerungsbasierte Screening- und Interventionsmaßnahmen entwickelt und eine Strategie zur personalisierten Demenzprävention realisiert werden können.

Motor skills of school-age children have an impact on learning, school results, and leading a healthy life. However, prevalence rates of motor developmental delays are increasing. Still there is a lack of understanding interrelationships between developmental domains of preschool aged children. We used data from the project “GIF MV”, a prospective dynamic cohort study. In this study, cross sectional data was used from the survey year 2023. To detect developmental delays of pre-schoolers a standardized, objective and valid screening method was used (“Dortmund Developmental Screening for Preschools-Revision (DESK 3–6 R)”). We determined associated variables for fine and gross motor developmental risks in preschoolers using Generalized Linear Mixed Models (n = 7,542 children). Fine motor risks were observed in 16.8

Health services research faces the challenge of providing sound recommendations for action for the further development of health systems and care. The application of causal inference methods offers health services researchers an excellent opportunity to identify causal relationships under everyday conditions. The role of clinical trials with a classic randomised controlled trial (RCT) design is recognised as suitable for gaining insights that help establish causal inference, but other methodological approaches to generating evidence also play an important role in health services research.The discussion paper presents key concepts and assumptions of causal inference and highlights their relevance for health services research. The paper makes it clear that in order to fulfil the assumptions, it is necessary to integrate theory, contextual knowledge, understanding of mechanisms and formal concepts, such as directed acyclic graphs (DAGs), into a suitable empirical study design. To this end, RCTs, quasi-experimental methods, causal machine learning, target trial emulation, in silico trials and the mixed-methods approach of integrated inference are presented and discussed in terms of their applicability in health services research and their internal and external validity.All of the approaches presented here can contribute to the estimation of causal effects when used in a targeted manner and in accordance with the central assumptions. Their suitability depends largely on the research question, data quality, theoretical modelling and contextual knowledge. The combination of complementary designs and high quality data sources can increase the robustness of causal conclusions.Causal inference in health services research is not only a methodological procedure, but an integrative process that systematically combines theory, methodology and contextual knowledge. By consistently linking these aspects, health services research can generate differentiated and actionable insights that go beyond correlative analyses and enable an understanding of the mechanisms of causal processes. This can lead, for example, to evidence-supported recommendations that critically examine the often non-evidence-based status quo and reliably evaluate the benefits of new models.

Abstract Iron deficiency assessment in myeloproliferative neoplasms is complicated by chronic inflammation, disease-related anemia, and treatment-induced changes in iron handling. We retrospectively analyzed 445 patients with MPN, including 158 with polycythemia vera, 97 with essential thrombocythemia, 44 with prefibrotic primary myelofibrosis, 127 with overt myelofibrosis, and 19 with MPN-unclassifiable, and compared conventional iron parameters with a population-based SHIP cohort of 4420 participants. ZPP was measured in the MPN cohort using quantitative fluorescence spectroscopy. Compared with SHIP, MPN patients had lower hemoglobin and higher ferritin, and the physiological positive correlation between ferritin and hemoglobin observed in SHIP was reversed in MPN patients, with R = 0.27, 95% CI 0.24 to 0.30, p < 0.001 in SHIP versus R = − 0.45, 95% CI − 0.52 to − 0.36, p < 0.001 in MPN. Median ZPP in the MPN cohort was 43.0 µmol/mol heme, with 123 of 445 patients (27.6%) showing ZPP values > 65 µmol/mol heme and 59 of 445 patients (13.3%) showing values > 100 µmol/mol heme. ZPP differed significantly between MPN entities, with median values of 35.0 µmol/mol heme in ET, 49.4 µmol/mol heme in PV, 36.5 µmol/mol heme in pre-PMF, 54.7 µmol/mol heme in overt MF, and 46.0 µmol/mol heme in MPN-U (p < 0.001). ZPP correlated inversely with hemoglobin in MPN patients (R = − 0.26, 95% CI − 0.35 to − 0.16, p < 0.001), whereas its association with ferritin was weak (R = − 0.10, 95% CI − 0.20 to − 0.00, p = 0.045). Among 80 patients with CTCAE grade ≥ 2 anemia, 58 (73%) had ZPP values above the upper limit of normal. In exploratory multivariable analysis, PV, overt MF, and phlebotomy were independently associated with higher ZPP, whereas CRP and time from diagnosis were not. In JAK2-mutated PV versus ET, ZPP was significantly higher in PV (48.5 versus 37.5 µmol/mol heme, p = 0.010), complementing lower transferrin saturation and higher JAK2 variant allele frequency. These data indicate that ZPP provides a functional readout of iron-restricted heme synthesis in MPN, adds information beyond ferritin and transferrin saturation, and may refine diagnostic reassessment and therapeutic monitoring, particularly in PV and overt MF.

Linking project data and data from routine clinical practice with healthcare-related data is essential for German healthcare research in order to answer complex questions validly and efficiently. Currently, fragmented data sources, heterogeneous legal requirements, and a lack of infrastructure prevent the optimal use and linking of these data. The Network University Medicine (NUM) is therefore developing a dedicated data infrastructure to link primary study data and routine clinical data with external healthcare-related data (e. g., data from statutory and private health insurance companies, data from cancer registries of the federal states, and data from registration offices). The position paper describes the various data worlds, including examples from epidemiological and clinical research that illustrate the added value and challenges of data linkage. In particular, it presents the new structures of the data acceptance and processing center (DAAeD) in the NUM, which is intended to enable quality-assured, data protection-compliant receipt and linkage of data. Standardized application and approval procedures as well as innovative privacy-preserving record linkage procedures are central to this. International experience, including from Scandinavia and the UK, demonstrates the benefits of such infrastructures for research and healthcare. In conclusion, we advocate rapid political and institutional implementation of the recommendations described in order to make health research in Germany competitive in international comparison and to ensure sustainable, patient-centered health care.

BACKGROUND:The German National Cohort (NAKO Gesundheitsstudie) is a prospective cohort study with 205 053 participants. Its goal is to identify risk factors for chronic diseases, including cancer. METHODS:We describe the methods of ascertaining cancer cases in NAKO (i.e., linkage with cancer registries and self-reporting), the incidence and prevalence figures obtained so far, and the ratios of observed to expected (O/E) case numbers. RESULTS:Case ascertainment identified 2774 existing cancer cases diagnosed within the five years prior to study enrollment and 4295 new cancer cases diagnosed up to five years after enrollment. Cancers of the breast, prostate, lung, and colorectum made up 55% of the incident cases. Fewer incident cases were found than would have been expected on the basis of incidences in the general population (O/E ratio 0.80, 95% confidence interval [0.76;0.83] for the first two-years of prospective follow-up); the O/E ratio varied across tumor sites (breast 1.02, prostate 1.12, lung 0.38, colorectum 0.62). Possible explanations include healthy volunteer bias, delayed reporting, as well as incomplete data collection from registries and self-reporting. CONCLUSION:Rising case numbers for the most common types of cancer are expected in the next few years and will enable comprehensive epidemiological analysis of the risk factors of cancer.

Background For early detection of breast cancer, clinical palpation of the breast is offered yearly to all women aged 30 and older, and the German Mammography Screening Programme (MSP) offers biennial mammograms to all women aged 50 to 75 years. We investigated the utilization of both screening methods across various migrant groups in Germany, as well as the effect of German language proficiency. Methods Cross-sectional data on participation frequencies from the baseline examination (2014 to 2019) of more than 100,000 women of the German National Cohort study (NAKO) were analysed by migrant status. Adjusted logistic regression analyses were conducted for palpation and MSP to compare screening uptake among six migrant groups, and non-migrant population. Results Palpation of the breast was less frequently utilized in all migrant groups with odds ratios ranging from 0.5 (95% CI 0.4-0.6) for Turkish women to 0.9 for women from western countries (95% CI 0.7-1.1) compared to autochthone Germans. Lower German language proficiency further decreases its use. In contrast, odds ratios for MSP participation did not differ substantially compared to Germans ranging from 0.8 to 1.2. German language proficiency had little effect on MSP participation. Discussion In contrast to earlier studies, our findings suggest that MSP participation and motivation does not significantly differ by migration status or language skills. This may indicate that information on MSP is broadly accessible through established invitation procedures in Germany. However, lower uptake of breast palpation by a physician in some migrant populations highlights potential gaps in broader preventive care engagement.

To collect sensitive patient data during clinical trials, the Informed Consent (IC) of the participants must be obtained beforehand. If the IC is not correct and complete, the document cannot be used to represent the will of the participant and will not be considered a legally valid document. However, few studies have examined the quality of the IC and the IC-quality found is unfortunately not satisfactory. The aim of this article is to describe the development of an IC quality assurance concept and to report the results of an evaluation using the example of a German Centre for Cardiovascular Research (DZHK) registry. All quality issues identified during the study were documented. These were aggregated into the quality indicators "Completeness", "Consistency of Data", "Correctness" and "Validity". Of 2,453 ICs, 1,588 had at least one quality issue; 99.8% of them were resolved. In addition, training sessions were conducted with study staff to raise awareness of the importance of correct IC collection, including documentation, and to minimize quality issues. Our data exemplify that improvements in the recording of ICs by the study staff can be achieved. This evaluation shows the value and importance of continuous IC quality control.

Abstract Background Informal caregivers provide a large part of the care required by people living with dementia. With disease progression, the burden on caregivers typically increases. Dyadic interventions, addressing both the caregiver and the person living with dementia simultaneously, can help to stabilize home care settings. This study examines the effectiveness and cost-effectiveness of an app-assisted dementia care intervention. Methods Living@home is a two-arm, randomized, controlled, multi-center interventional study designed to evaluate the effectiveness of a dyadic, app-based intervention on home care stability as well as the cost-effectiveness of this approach. The inclusion criteria are a formal diagnosis of dementia and living in their own home for the person with dementia, as well as access to a smartphone and internet for the informal caregiver. A total of 554 dyads will be recruited in five participating memory clinics and randomized (1:1 ratio, using block randomization) into either the intervention or the control group. The intervention group will receive personalized dementia care management for a period of 12 months. A mobile health app connecting caregivers with a Family Care Specialist offers informal caregivers access to memory clinics and Care Specialists at any time, monitoring of their health situation through real-time data collection, overview of care-related tasks, information and alerts tailored to the reported individual caregiver burden. The control group receives care-as-usual. Both groups will be assessed at baseline and after 12 months. The primary outcome is the caregiver’s perseverance time (Perseverance Time Scale), and crucial secondary supportive outcomes are neuropsychiatric symptoms in the person living with dementia (Neuropsychiatric Inventory), and the caregiver’s perceived burden (Zarit Burden Interview). Further secondary outcomes include the caregiver’s resilience and self-efficacy, the dyads’ physiological stress level (as measured by hair cortisol concentrations), health-related quality of life, caregiver depression and anxiety, dyads’ unmet needs, and cost-effectiveness. Intervention effects will be estimated by using multivariate regression analyses. Discussion Evidence on the effectiveness and cost-effectiveness of the intervention created from this study can help to inform decision makers and support the transition of the intervention to standard care. Trial registration ClinicalTrials.gov NCT07251088, Registered 25.11.2025

Scientists working with cancer registry data are often confronted with large proportions of missing values in ordinal variables, such as tumor stage, grading or the general health status (ECOG-PS scored 0 to 5). Despite the long-standing issue, research on handling missing ordinal cancer registry data remains sparse. A simulation study was conducted using complete lung cancer cases (2019–2022) from the North Rhine-Westphalia Cancer Registry. Missing values in ECOG-PS were generated with varying missingness mechanisms (MCAR, MAR, MNAR), missingness proportions (10

BACKGROUND:Patient-Reported Outcomes (PROs) in personalized lung cancer care aim to facilitate a targeted therapeutic management approach. This study explores the implementation of PROs as an intervention component within a precision medicine program, with a focus on identifying facilitating factors and barriers from the perspectives of health care providers (HCPs) and patients with stage IV non-small-cell lung cancer (NSCLC). METHODOLOGY:Semi-structured individual interviews were conducted with HCPs and NSCLC patients over two rounds in 2023 and 2024, respectively. Verbatim transcripts were analyzed using qualitative content analysis. The framework of Grol and Wensing was employed, which divides healthcare into six dimensions. RESULTS:The structured documentation of symptoms and quality of life constitutes a benefit in that it enables intervention by the treating physician. From the perspective of HCPs, incorporating PROs into daily clinical practice was associated with considerable organizational challenges and the need for logins into an additional system to access the results. This required a substantial investment of time and personnel, which resulted in a lack of acceptance. The predominant motivation of patients who participated in the PRO questionnaires was a desire to contribute to scientific research. In general, the regular administration of the questionnaire has proven unfeasible for the NSCLC cohort, given the high disease burden often experienced in stage IV. CONCLUSIONS:Despite implementation challenges, PROs can improve symptom monitoring, communication, and patient-centered care in advanced NSCLC when key barriers are addressed.

Recent studies have suggested a potential association of particulate matter (PM) and noise with diabetes and obesity, but studies examining other environmental exposures and their sex-specific and joint associations remain limited. Therefore, we investigated sex-specific individual and joint associations of annual exposure to multiple environmental factors with diabetes and obesity-related measures using cross-sectional data from the population-based multi-center German National Cohort (NAKO). Outcomes included self-reported diabetes mellitus, body mass index (BMI), obesity (BMI ≥30 kg/m2), and waist circumference. Annual mean residential exposures included air pollutants, air temperature, day-evening-night road traffic noise (Lden) and surrounding greenness (normalized difference vegetation index (NDVI)). We used sex-stratified linear and logistic regression models to assess individual associations and quantile g-computation to assess joint associations. Among 174,955 adult participants (50.4% women), 5.6% reported a diabetes diagnosis and 20.9% were obese. An interquartile range increase in PM2.5 and Lden was consistently associated with diabetes and obesity-related measures (e.g., PM2.5-diabetes for men: odds ratio (OR) [95% confidence interval] = 1.12 [1.02; 1.22]; Lden-BMI for women: 0.22 kg/m2 [0.16; 0.27]). Greenness showed non-linear (inverted U-shaped) with all outcomes. An interquartile range increase in multiple exposures simultaneously was associated with higher odds of diabetes, obesity and higher obesity-related measures (e.g., mixture (PM2.5,Lden, lack of NDVI)-diabetes: OR = 1.20 [1.09; 1.33] for men; mixture (PM2.5,Lden, lack of NDVI)-BMI: 0.33 kg/m2 [0.21; 0.44] for women). While longitudinal studies need to confirm these findings, the study highlights that reducing multiple adverse environmental exposures could be potential targets for the prevention of diabetes and obesity.

BACKGROUND AND OBJECTIVES:Ageing populations in high-income countries reduce the proportion of potential blood donors while increasing transfusion demand. Sustaining an adequate blood supply requires higher donor motivation among younger age groups. We analysed long-term trends in whole blood donations (WBDs) in one German federal state as an indicator for challenges that may arise in other high-income countries. MATERIALS AND METHODS:In our prospective longitudinal study (starting 2005), we obtained the age and sex of the donors of all WBDs in the German federal state Mecklenburg-Western Pomerania in 2019 and 2020 and compared them with the data from 2005 to 2015. Population data from the German statistical office were used to predict future WBD in two models, population-based and population-based with behaviour-adjusted prediction. RESULTS:WBD decreased from 118,419 in 2005 to 83,871 in 2019 (-29.2%) and 76,912 in 2020 (-35.1%). Donation rates per 1000 inhabitants declined by 19.1% between 2005 and 2019, indicating a loss of donor motivation beyond demographic effects. Based on the donation numbers of 2019, we predict a further decline of WBD in 2030 by -12.7% (population-based projection) or -15.1% (behaviour-adjusted projection), respectively. CONCLUSION:The decline in blood donations is no longer solely driven by demographic changes but also by reduced motivation among younger donors. As ageing populations and changing donor behaviour are common to many high-income countries, these findings likely reflect an emerging international trend. Targeted strategies to recruit and retain young donors are urgently needed to ensure sustainable blood supplies in ageing societies.