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Abstract Background People with "Differences of Sex Development" (DSD) require comprehensive, specialised, and individualised medical and psychological care. This is often perceived as inadequate by those affected. Therefore, the German Federal Ministry of Health funded the project DSDCare which aimed to improve the quality of care for people with DSD over the lifespan in Germany. Method Indicators of structural, process, and outcome quality were defined, which are used to evaluate the quality of care. The indicators of structural quality are collected once a year from ten participating centres. Based on the "Open Source Registry System for Rare Diseases (OSSE)", a DSD-specific registry (DSDReg) was developed, in which patient-related care data are recorded in order to be able to assess the process and outcome quality. Furthermore, patient-reported outcomes are collected directly from the patients by means of questionnaires. The data are reported back to the participating centres in an annual benchmarking. Results Twenty-five indicators of structural quality were defined, twelve indicators of process quality and ten of outcome quality. A total of 477 patients were registered in DSDReg in the period from May 2021 till October 2022. The mean age is 16 years; the most common diagnosis groups are 46,XY DSD (34.8%), followed by 46,XX DSD (33.3%) and chromosomal DSD (27.5%). Patient numbers vary across centres from N = 10 to N = 131. Questionnaires are available from 316 (66.2%) affected individuals, including 122 from adults, 120 from children or adolescents with DSD, and 191 from parents. Preliminary results show heterogeneity between centres in both data quality and quality of care. Conclusions The DSDReg is well established in the DSDCare project as a quality assurance tool with continuously increasing recruitment figures. The implemented quality indicators are applicable, enable a comparison between the participating centres and will foreseeably lead to an improvement of the care of patients with DSD. A long-term continuation of the registry after the end of the initial study period is therefore indicated.

Abstract Background In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional “treatment as usual” (TAU). Methods A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient’s individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness. Discussion This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice. Trial registration German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.

Abstract Background Generating synthetic patient data is crucial for medical research, but common approaches build up on black-box models which do not allow for expert verification or intervention. We propose a highly available method which enables synthetic data generation from real patient records in a privacy preserving and compliant fashion, is interpretable and allows for expert intervention. Methods Our approach ties together two established tools in medical informatics, namely OMOP as a data standard for electronic health records and Synthea as a data synthetization method. For this study, data pipelines were built which extract data from OMOP, convert them into time series format, learn temporal rules by 2 statistical algorithms (Markov chain, TARM) and 3 algorithms of causal discovery (DYNOTEARS, J-PCMCI+, LiNGAM) and map the outputs into Synthea graphs. The graphs are evaluated quantitatively by their individual and relative complexity and qualitatively by medical experts. Results The algorithms were found to learn qualitatively and quantitatively different graph representations. Whereas the Markov chain results in extremely large graphs, TARM, DYNOTEARS, and J-PCMCI+ were found to reduce the data dimension during learning. The MultiGroupDirect LiNGAM algorithm was found to not be applicable to the problem statement at hand. Conclusion Only TARM and DYNOTEARS are practical algorithms for real-world data in this use case. As causal discovery is a method to debias purely statistical relationships, the gradient-based causal discovery algorithm DYNOTEARS was found to be most suitable.

Background: Due to the large number of radiotherapeutic options for treatment of posterior uveal melanoma (UM), advantages of each option regarding important clinical endpoints have yet to be determined. Therefore, objective of this systematic review was to analyze the numerous pro- and retrospective cohort studies focusing on the efficacy of different radiotherapeutic options for UM in adults, considering local tumor control, overall survival, visual acuity, eye preservation, metastasis, radiation side effects and dose rates. Methods: The Review was performed based on the Cochrane Handbook of Systematic Reviews. The PubMed database was searched for studies published from January 1st, 2000, up to December 31st, 2021. Research, study selection and critical appraisal was performed by two reviewers. The risk of bias assessment was performed through the revised Cochrane risk of bias tools RoB 2 and ROBINS-I. A meta-analysis of proportions was performed using R (R version 4.1.3, library: meta, procedure: metaprop). This systematic review was registered with Prospero (ID CRD42022311758). Results: Of 4886 studies identified in the database, a total of 20 studies with 4979 participants were included in the qualitative synthesis. Through critical appraisal with ROBINS-I and RoB 2, studies received a ‘moderate’, ‘serious’ or ‘some concerns’ overall risk of bias. Heterogeneity analysis allowed for meta-analysis of proportion of 3 outcome-therapy combinations: local tumor control with I-125 Brachytherapy (proportion: 0.94, CI 95 %: 0.91–0.98), local tumor control with proton therapy (proportion: 0.96, CI 95 %: 0.92–1.00) and eye preservation with I-125 brachytherapy (proportion: 0.91, CI 95 %: 0.88–0.93). This shows local tumor control to be at 94 % with I-125 brachytherapy and at 96 % with proton therapy, as well as an eye preservation rate of 91 % with I-125 brachytherapy. Discussion: The evaluation of outcomes of radiotherapy in UM is limited because of missing data on radiation doses as well as great heterogeneity of study protocols. Radiation therapy outcomes are so far not comparable. Therefore, we recommend for upcoming studies on this topic to provide the biological effective dose (BED) or the equivalent dose in 2 Gy fractions (EQD2) per eye structure, thereby enabling a comparison of outcomes of different forms of radiation therapy.

Non-pharmaceutical interventions (NPI) have been proven successful in a population-based approach to protect from SARS-CoV-2 transmission during the COVID-19 pandemic. As a consequential-effect, a reduction in the spread of all respiratory viruses has been observed, but the primary factors behind this phenomenon have yet to be identified. We conducted a subgroup analysis of participants from the ELISA study, a prospective longitudinal cohort study on SARS-CoV-2 transmission, at four timepoints from November 2020 – September 2022. The aim was to provide a detailed overview of the circulation of respiratory viruses over 2 years and to identify potential personal risk factors of virus distribution. All participants were screened using qPCR for respiratory viral infections from nasopharyngeal swabs and answered a questionnaire regarding behavioral factors. Several categories of risk factors for the transmission of respiratory viruses were evaluated using a scoring system. In total, 1,124 participants were included in the study, showing high adherence to governmental-introduced NPI. The overall number of respiratory virus infections was low (0–4.9% of participants), with adenovirus (1.7%), rhino−/enterovirus (3.2%) and SARS-CoV-2 (1.2%) being the most abundant. We detected an inverse correlation between the number and intensity of NPI and the number of detected respiratory viruses. More precisely, the attendance of social events and household size was associated with rhino−/enterovirus infection while social contacts were associated with being positive for any virus. NPI introduced during the COVID-19 pandemic reduced the occurrence of seasonal respiratory viruses in our study, showing different risk-factors for enhanced transmission between viruses.Trial registrationDRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00023418, Registered on 28 October 2020.

Abstract Background A national colorectal cancer (CRC) screening programme was launched in 2002 in Germany. A comprehensive evaluation of the programme effectiveness using real-world data is still lacking. In addition, there are regional reports on increasing colorectal cancer incidence in younger populations. Therefore, we aimed to describe and compare the overall, age- and stage-specific incidence trends for colorectal, colon and rectal cancer. Methods We used data from seven population-based cancer registries in Germany. We report absolute and relative changes in incidence rates between the early screening phase (2003–2005) and the most recent time period available (2015–2017), as well as annual percent changes. We analysed incidences according to tumour site (colorectum, colon, and rectum) and to six age groups (young adults: 15–34, 35–39, 40–49, screening-entitled/older adults: 50–54, 55–69 and 70 + years old). Results In our sample of 271,011 colorectal adenocarcinomas, about two-thirds were located in the colon and 95% of them occurred in the age group 50+ (50–54: 5%, 55–69: 32.8%, 70+: 57.2%). For the time period 2003–2005 the age-specific incidence rates of individuals in the age group 55–69 were about 76/100,00 for colon and 54/100,000 for rectal cancer (age group 70 + colon: 179/100,000; rectum: 84/100,000). The incidence rates in young adults were less than 13% of that of individuals in the age group 55–69 (

Background: Approximately 27% of female breast cancer patients are diagnosed before the age of 55, a group often comprising mothers with young children. Maternal psychosocial well-being significantly impacts these children’s psychosocial well-being. This study assesses the well-being of children with mothers who have early-onset breast cancer. Methods: We examined the eldest child (up to 15 years old) of women with nonmetastatic breast cancer (

Abstract Background Scientists, physicians, and the general public legitimately expect scholarly publications to give true answers to study questions raised. We investigated whether findings from studies published in journals with higher Journal Impact Factors (JIFs) are closer to truth than findings from studies in less-cited journals via a meta-epidemiological approach. Methods We screened intervention reviews from the Cochrane Database of Systematic Reviews (CDSR) and sought well-appraised meta-analyses. We used the individual RCT study estimates’ relative deviation from the pooled effect estimate as a proxy for the deviation of the study results from the truth. The effect of the JIF on the relative deviation was estimated with linear regression and with local polynomial regression, both with adjustment for the relative size of studies. Several sensitivity analyses for various sub-group analyses and for alternative impact metrics were conducted. Results In 2459 results from 446 meta-analyses, results with a higher JIF were on average closer to “truth” than the results with a lower JIF. The relative deviation decreased on average by −0.023 per JIF (95% CI −0.32 to −0.21). A decrease was consistently found in all sensitivity analyses. Conclusions Our results indicate that study results published in higher-impact journals are on average closer to truth. However, the JIF is only one weak and impractical indicator among many that determine a studies’ accuracy.

Byline: Darko. Katalinic, Ivan. Aleric, Martina. Smolic, Aleksandar. Vcev Chronic migraine (CM) is a neurological disorder that impacts up to 2.2% of the population worldwide and imposes a significant socioeconomic [...]

IntroductionComparable indicators on complete cancer prevalence are increasingly needed in Europe to support survivorship care planning. Direct measures can be biased by limited registration time and estimates are needed to recover long term survivors. The completeness index method, based on incidence and survival modelling, is the standard most validated approach.MethodsWithin this framework, we consider two alternative approaches that do not require any direct modelling activity: i) empirical indices derived from long established European registries; ii) pre-calculated indices derived from US-SEER cancer registries. Relying on the EUROCARE-6 study dataset we compare standard vs alternative complete prevalence estimates using data from 62 registries in 27 countries by sex, cancer type and registration time.ResultsFor tumours mostly diagnosed in the elderly the empirical estimates differ little from standard estimates (on average less than 5% after 10-15 years of registration), especially for low prognosis cancers. For early-onset cancers (bone, brain, cervix uteri, testis, Hodgkin disease, soft tissues) the empirical method may produce substantial underestimations of complete prevalence (up to 20%) even when based on 35-year observations. SEER estimates are comparable to the standard ones for most cancers, including many early-onset tumours, even when derived from short time series (10-15 years). Longer observations are however needed when cancer-specific incidence and prognosis differ remarkably between US and European populations (endometrium, thyroid or stomach).DiscussionThese results may facilitate the dissemination of complete prevalence estimates across Europe and help bridge the current information gaps.

Abstract Background Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups. Methods In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis. Results In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, p adjusted

Abstract Background In Germany, CRT devices with defibrillator capability (CRT-D) have become the predominant treatment strategy for patients with heart failure and cardiac dyssynchrony. However, according to current guidelines, most patients would also be eligible for the less expensive CRT pacemaker (CRT-P). We conducted a cost-effectiveness analysis for CRT-P devices compared to CRT-D devices from a German payer’s perspective. Methods Longitudinal health claims data from 3569 patients with de novo CRT implantation from 2014 to 2019 were used to parametrise a cohort Markov model. Model outcomes were costs and effectiveness measured in terms of life years. Transition probabilities were derived from multivariable parametric survival regression that controlled for baseline differences of CRT-D and CRT-P patients. Deterministic and probabilistic sensitivity analyses were conducted. Results The Markov model predicted a median survival of 84 months for CRT-P patients and 92 months for CRT-D patients. In the base case, CRT-P devices incurred incremental costs of € − 13,093 per patient and 0.30 incremental life years were lost. The ICER was € 43,965 saved per life year lost. In the probabilistic sensitivity analysis, uncertainty regarding the effectiveness was observed but not regarding costs. Conclusion This modelling study illustrates the uncertainty of the higher effectiveness of CRT-D devices compared to CRT-P devices. Given the difference in incremental costs between CRT-P and CRT-D treatment, there would be significant potential cost savings to the healthcare system if CRT-D devices were restricted to patients likely to benefit from the additional defibrillator.