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Zusammenfassung Hintergrund Als Bundesland mit dem höchsten Altersdurchschnitt in Deutschland und besonderen Strukturmerkmalen ländlich geprägter Gebiete sind die Folgen des demographischen Wandels bereits heute in Sachsen spürbar. Um die medizinische Versorgung von Parkinson-Patienten zu verbessern, bedarf es einer Status-quo-Analyse der aktuellen Versorgungspraxis. Ziel der Arbeit (Fragestellung) Inwieweit unterscheidet sich die Inanspruchnahme der medizinischen Leistungserbringung von Parkinson-Patienten im Vergleich von städtisch und ländlich geprägten Gebieten sowie im Vergleich von Parkinson-Patienten mit und ohne Neurologenkontakt im Beobachtungszeitraum von 2011 bis 2019? Material und Methoden Die Kohortenstudie basiert auf umfangreichen Routinedaten der Krankenkasse AOK PLUS der Jahre 2010 bis 2019 für Sachsen. Untersucht wurde eine Kohorte von insgesamt 15.744 Parkinson-Patienten (n = 67.448 Patientenjahre) und eine gematchte Vergleichskohorte (n = 674.480 Patientenjahre; Kriterien: Geburtsjahr, Geschlecht, Versicherungsjahr, Wohnsitz Stadt/Land) ohne ICD-10-Kodierung einer Bewegungsstörung. Ergebnisse Insgesamt war eine kontinuierliche Zunahme der Anzahl der Erkrankten in der dynamischen Kohorte von 2011 (n = 6829) bis 2019 (n = 8254) zu beobachten. Stadt-Land-Unterschiede zeigten sich insbesondere in der geringeren (Mit‑)Behandlung durch niedergelassene Neurologen in ländlich geprägten Gebieten. Parkinson-Patienten hatten ein 3,5- bzw. 4‑fach erhöhtes Risiko zu versterben im Vergleich zu Versicherten der Vergleichskohorte. Veränderungen der medikamentösen Parkinson-Therapie (Zunahme COMT- und MAO-Inhibitoren) sowie der Heilmittelerbringung (Zunahme Ergotherapie und Logopädie) über die Beobachtungszeit zeigten sich primär bei Parkinson-Patienten mit Neurologenkontakt. Diskussion In der Studie konnten eine erhöhte Morbidität und Mortalität bei Parkinson-Patienten identifiziert werden, die sich als Ziel für innovative Versorgungskonzepte eignen. Die zunehmende Zahl an Patienten und die beschriebenen Unterschiede dokumentieren hierfür den Bedarf. Gleichzeitig zeigen die Veränderungen in der Verordnungspraxis, dass innovative Therapien von niedergelassenen Neurologen eingesetzt werden.

Purpose Most individuals with antibody deficiency (hypogammaglobulinemia) need immunoglobulin replacement therapy (IgG-RT) from healthy plasma donors to stay clear of infections. However, a small subset of hypogammaglobulinemic patients do not require this substitution therapy. We set out to investigate this clinical conundrum by asking whether the peripheral B cell receptor repertoires differ between antibody-deficient patients who do and do not need IgG-RT. Methods We sequenced and analyzed IgG and IgM heavy chain B cell receptor repertoires from peripheral blood mononuclear cells (PBMCs) isolated from patients with low serum IgG concentrations who did or did not require IgG-RT. Results Compared to the patients who did not need IgG-RT, those who needed IgG-RT had higher numbers of IgG antibody clones, higher IgM diversity, and less oligoclonal IgG and IgM repertoires. The patient cohorts had different heavy chain variable gene usage, and the patients who needed IgG-RT had elevated frequencies of IgG clones with higher germline identity (i.e., fewer somatic hypermutations). Conclusion Antibody-deficient patients with infection susceptibility who needed IgG-RT had more diverse peripheral antibody repertoires that were less diverged from germline and thus may not be as optimal for targeting pathogens, possibly contributing to infection susceptibility.

Patients with inborn errors of the alternative NF-κB pathway have low thymic AIRE expression, leading to the development of auto-Abs neutralizing type I IFNs, and severe viral diseases.

Funding Information: The documentation specialist S.E-H. was funded by the Federal Ministry of Education and Research (BMBF, Support Code: 01GM1517C), by the European Society for Immunodeficiencies (ESID), 2018, by the Care-for-Rare Foundation, by PROimmun e.V., and by a restricted grant from LFB, CSL Behring, and Grifols. For GAIN, she was funded by the BMBF (GAIN support code: 01GM1910A). For RESIST, she was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2155 - project number 390874280. M.K. is supported by the Deutsche Forschungsgemeinschaft (DFG) SFB1160_2 as clinician scientist associated to IMM-PACT-Program, Faculty of Medicine, University of Freiburg, Freiburg, Germany. The views expressed in the submitted article are those of the authors’ and not an official position of their institutions or funders. Publisher Copyright: © 2023, The Author(s). Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3–28) and the median delay from onset to diagnosis was 5 years (IQR 1–14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options. publishersversion epub_ahead_of_print

A pandemia do coronavírus (COVID-19) causou uma mudança brusca na vida da população, sobretudo pelo medo da contaminação pelo vírus SARS-CoV-2, desse modo, o isolamento social foi adotado como medida de controle para atenuar a transmissão viral. Este contexto gerou um ambiente desfavorável, que culminou com o desenvolvimento ou piora do quadro clínico dos pacientes com Transtorno Obsessivo Compulsivo (TOC).Este estudo tem comoobjetivoanalisar a influência da pandemia do COVID-19 nos casos de TOC. Para elaborar estarevisão de literatura, buscou-se artigos indexados nas plataformasScieloePubmed, usando os descritores “Obsessive-CompulsiveDisorder” e “Covid-19” e sendo usado o operador booleano “AND”. Foram incluídos artigos publicados entre 2020 e 2022, em inglês e português e de acesso livre, excluiu-se aqueles que não se enquadravam em tais critérios e à temática, dessa maneira obtendo-se 113 artigos. Na seleção dos artigos a serem analisados, 32 se enquadraram na primeira etapa e, por fim, seguindo os critérios de inclusão e exclusão após leitura minunciosa, a etapa final contou com 18 artigos para análise.Assim, foi inferido que pandemias globais como a COVID-19 podem representar um fardo substancial para pacientes com TOC relacionado à contaminação. Embora, o impacto da atual pandemia no TOC não seja totalmente conhecido, é possível que o transtorno possa levar de semanasa meses para se tornar aparente, e nota-se um grande risco de recorrência ou exacerbação dos sintomas em alguns pacientes. Entretanto, deve-se considerar que a análise do quadro clínico sofreu influência do período da pandemia que o estudo foi realizado e em que país ocorreu, observando-se manifestações tanto de piora quanto de melhora, a depender dessas variáveis. Contudo, notou-se que, de maneira geral, o foco excessivo da mídia e sociedade na prevenção da contaminação e a normalização dos rituais de descontaminação reforçaram os comportamentos disfuncionais compulsivos.Ademais, no contexto pandêmico existem vários mecanismos pelos quais o TOC pode se agravar, como a dinâmica familiar alterada, que de maneira implícita pode incentivar rituais extremos de descontaminação, proporcionar um ambiente mais estressante e ansiogênico para lidar com os medos relacionados ao vírus.Além disso, estressores financeiros gerados pela insegurança da economia mundial e o isolamento social, podem contribuir para a ansiedade patológica, associado ao estresse, e gerar sintomas depressivos, propiciando hábitos cada vez mais inflexíveis de limpeza e efetivamente obsessivos.Alguns estudos procuraram relacionar o medo e a instabilidade pandêmica de acordo com a faixa etária, sobretudo em estudantes, atribuindo novos diagnósticos de TOC e a sua exacerbação, decorrentes do objetivo de conter a contaminação.Além do mais, a respeito do tratamentoforam identificadascertas medidas para enfrentamento do TOC, como por exemplo, mudanças de estilo de vida, aderência a terapia farmacológicade primeira linha, a qualsão os inibidores seletivos da recaptação de serotonina (ISRS), e da psicoterapia, especialmente a modalidade cognitivo comportamental (TCC).Portanto,a exacerbação do TOC diante da pandemia daCOVID-19 apresenta-se presente, embora a extensão dos diferentes sintomas varie,é de total importânciaque os profissionais da saúde reconheçam este cenário parapromover a aderência ao tratamento medicamentoso e não medicamentoso, melhorando a qualidade de vida dessa população.&nbsp

ZusammenfassungDie Umstellung auf das Pflegebudget bedeutet für die Krankenhäuser veränderte Verhandlungen mit den Krankenkassen. Dabei geht es um klinikindividuelle Pflegekosten – und damit um viel Geld. Erfahren Sie mehr über Inhalte und Verhandlungsstrategien.

Background General practitioners (GPs) play a key role in the provision of primary palliative care (PC). The identification of patients who might benefit from PC and the timely initiation of patient-centred PC measures at the end of life are essential, yet challenging. Although different tools exist to support these key tasks, a structured approach is often missing. Objective The study aimed at implementing the German version of the Supportive and Palliative Care Indicators Tool (SPICT-DE™) in general practices, following a structured and regional approach, in order to evaluate the effects of this tool on the identification of patients with potential PC needs and the initiation of patient-centred PC measures. Methods The intervention of this mixed-methods study comprised a standardised training of 52 GPs from 34 general practices in two counties in Lower Saxony, Germany, on the use of the SPICT-DE™. The SPICT-DE™ is a clinical tool which supports the identification of patients with potential PC needs. Subsequently, over a period of 12 months, GPs applied the SPICT-DE™ in daily practice with adult patients with chronic, progressive diseases, and completed a follow-up survey 6 months after the initial patient assessment. The outcome parameters were alterations in the patient’s clinical situation, and the type and number of initiated patient-centred PC measures during the follow-up interval. Additionally, 12 months after the standardised training, GPs provided feedback on their application of the SPICT-DE™. Results A total of 43 GPs (n = 15 female, median age 53 years) out of an initial sample of 52 trained GPs assessed 580 patients (n = 345 female, median age 84 years) with mainly cardiovascular (47%) and cancer (33%) diseases. Follow-up of 412 patients revealed that 231 (56%) experienced at least one critical incident in their disease progression (e.g. acute crisis), 151 (37%) had at least one hospital admission, and 141 (34%) died. A review of current treatment/medication (76%) and a clarification of treatment goals (53%) were the most frequently initiated patient-centred PC measures. The majority of GPs deemed the SPICT-DE™ practical (85%) and stated an intention to continue applying the tool in daily practice (66%). Conclusions The SPICT-DE™ is a practical tool that supports the identification of patients at risk of deterioration or dying and promotes the initiation of patient-centred PC measures. Trial registration The study was registered in the German Clinical Trials Register (N° DRKS00015108; 22/01/2019).

Zusammenfassung. Die hier vorgestellte Studie nimmt aus einer praxeologischen Perspektive empirisch in den Blick, wie Multiprofessionalität unter dem Anspruch von Inklusion in Kindertageseinrichtungen für Kinder mit und ohne Behinderung hervorgebracht wird. Erste Erkenntnisse aus der Analyse von Gruppendiskussionen mit Kita-Teams verweisen auf Spannungsverhältnisse zwischen einer normativen Orientierung am Gleichheitsanspruch der Inklusionsidee und der mehrperspektivischen Realisierung in hierarchisch (vor-)strukturierten Räumen. Als zentrale Orientierungsfigur in der Bearbeitung dieser Spannungsverhältnisse zeigt sich ein Modus des Austarierens von Diskrepanzen.

Retinoid X receptor (RXR) plays a pivotal role as a transcriptional regulator and serves as an obligatory heterodimerization partner for at least 20 other nuclear receptors (NRs). Given a potentially limiting/sequestered pool of RXR and simultaneous expression of several RXR partners, we hypothesized that NRs compete for binding to RXR and that this competition is directed by specific agonist treatment. Here, we tested this hypothesis on three NRs: peroxisome proliferator-activated receptor gamma (PPARγ), vitamin D receptor (VDR), and retinoic acid receptor alpha (RARα). The evaluation of competition relied on a nuclear translocation assay applied in a three-color imaging model system by detecting changes in heterodimerization between RXRα and one of its partners (NR1) in the presence of another competing partner (NR2). Our results indicated dynamic competition between the NRs governed by two mechanisms. First, in the absence of agonist treatment, there is a hierarchy of affinities between RXRα and its partners in the following order: RARα > PPARγ > VDR. Second, upon agonist treatment, RXRα favors the liganded partner. We conclude that recruiting RXRα by the liganded NR not only facilitates a stimulus-specific cellular response but also might impede other NR pathways involving RXRα.

Background General practitioners (GPs) play a crucial role in the provision of end-of-life care (EoLC). The present study aimed at comparing the quality of GPs’ EoLC before and after an intervention involving a clinical decision aid and a public campaign. Methods The study was part of the larger interventional study ‘Optimal care at the end of life’ (OPAL) (Innovation Fund, Grant No. 01VSF17028). The intervention lasted 12 months and comprised two components: (1) implementation of the Supportive and Palliative Care Indicators Tool (SPICT-DE™) in general practice and (2) a public campaign in two German counties to inform and connect regional health care providers and stakeholders in EoLC. Participating GPs completed the General Practice End of Life Care Index (GP-EoLC-I) pre- (t0) and post- (t1) intervention. The GP-EoLC-I (25 items, score range: 14–40) is a self-assessment questionnaire that measures the quality of GPs’ EoLC. It includes two subscales: practice organisation and clinical practice. Data were analysed descriptively, and a paired t-test was applied for the pre–post comparison. Results Forty-five GPs (female: 29%, median age: 57 years) from 33 general practices participated in the intervention and took part in the survey at both times of measurement (t0 and t1). The mean GP-EoLC-I score (t0 = 27.9; t1 = 29.8) increased significantly by 1.9 points between t0 and t1 (t(44) = − 3.0; p = 0.005). Scores on the practice organisation subscale (t0 = 6.9; t1 = 7.6) remained almost similar (t(44) = -2.0; p = 0.057), whereas those of the clinical practice subscale (t0 = 21.0; t1 = 22.2) changed significantly between t0 and t1 (t(44) = -2.6; p = 0.011). In particular, items regarding the record of care plans, patients’ preferred place of care at the end of life and patients’ preferred place of death, as well as the routine documentation of impending death, changed positively. Conclusions GPs’ self-assessed quality of EoLC seemed to improve after a regional intervention that involved both the implementation of the SPICT-DE™ in daily practice and a public campaign. In particular, improvement related to the domains of care planning and documentation. Trial registration The study was registered in the German Clinical Trials Register (DRKS00015108; 22/01/2019).

Symptoms of Parkinson’s disease (PD) can be controlled well, but treatment often requires expert judgment. Telemedicine and sensor-based assessments can allow physicians to better observe the evolvement of symptoms over time, in particular with motor fluctuations. In addition, they potentially allow less frequent visits to the expert’s office and facilitate care in rural areas. A variety of systems with different strengths and shortcomings has been investigated in recent years. We designed a multimodal telehealth intervention (TelePark) to mitigate the shortcomings of individual systems and assessed the feasibility of our approach in 12 patients with PD over 12 weeks in preparation for a larger randomized controlled trial. TelePark uses video visits, a smartphone app, a camera system, and wearable sensors. Structured training included setting up the equipment in patients’ homes and group-based online training. Usability was assessed by questionnaires and semi-standardized telephone interviews. Overall, 11 out of 12 patients completed the trial (5 female, 6 male). Mean age was 65 years, mean disease duration 7 years, mean MoCA score 27. Adherence was stable throughout the study and 79% for a short questionnaire administered every second day, 62% for medication confirmation, and 33% for an electronic Hauser diary. Quality of life did not change in the course of the study, and a larger cohort will be required to determine the effect on motor symptoms. Interviews with trial participants identified motivations to use such systems and areas for improvements. These insights can be helpful in designing similar trials.

The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required.To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019?The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder.Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4‑fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist.The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care.HINTERGRUND: Als Bundesland mit dem höchsten Altersdurchschnitt in Deutschland und besonderen Strukturmerkmalen ländlich geprägter Gebiete sind die Folgen des demographischen Wandels bereits heute in Sachsen spürbar. Um die medizinische Versorgung von Parkinson-Patienten zu verbessern, bedarf es einer Status-quo-Analyse der aktuellen Versorgungspraxis.Inwieweit unterscheidet sich die Inanspruchnahme der medizinischen Leistungserbringung von Parkinson-Patienten im Vergleich von städtisch und ländlich geprägten Gebieten sowie im Vergleich von Parkinson-Patienten mit und ohne Neurologenkontakt im Beobachtungszeitraum von 2011 bis 2019?Die Kohortenstudie basiert auf umfangreichen Routinedaten der Krankenkasse AOK PLUS der Jahre 2010 bis 2019 für Sachsen. Untersucht wurde eine Kohorte von insgesamt 15.744 Parkinson-Patienten (n = 67.448 Patientenjahre) und eine gematchte Vergleichskohorte (n = 674.480 Patientenjahre; Kriterien: Geburtsjahr, Geschlecht, Versicherungsjahr, Wohnsitz Stadt/Land) ohne ICD-10-Kodierung einer Bewegungsstörung.Insgesamt war eine kontinuierliche Zunahme der Anzahl der Erkrankten in der dynamischen Kohorte von 2011 (n = 6829) bis 2019 (n = 8254) zu beobachten. Stadt-Land-Unterschiede zeigten sich insbesondere in der geringeren (Mit‑)Behandlung durch niedergelassene Neurologen in ländlich geprägten Gebieten. Parkinson-Patienten hatten ein 3,5- bzw. 4‑fach erhöhtes Risiko zu versterben im Vergleich zu Versicherten der Vergleichskohorte. Veränderungen der medikamentösen Parkinson-Therapie (Zunahme COMT- und MAO-Inhibitoren) sowie der Heilmittelerbringung (Zunahme Ergotherapie und Logopädie) über die Beobachtungszeit zeigten sich primär bei Parkinson-Patienten mit Neurologenkontakt.In der Studie konnten eine erhöhte Morbidität und Mortalität bei Parkinson-Patienten identifiziert werden, die sich als Ziel für innovative Versorgungskonzepte eignen. Die zunehmende Zahl an Patienten und die beschriebenen Unterschiede dokumentieren hierfür den Bedarf. Gleichzeitig zeigen die Veränderungen in der Verordnungspraxis, dass innovative Therapien von niedergelassenen Neurologen eingesetzt werden.

Background Demographic trends show an increasing number of elderly people and thus a growing need for palliative care (PC). Such care is increasingly being provided by long-term care (LTC) facilities. The present study aimed at exploring PC indicators of residents at LTC facilities belonging to a non-profit provider in Lower Saxony, Germany, in order to identify potential improvements. Methods A descriptive cross-sectional study was conducted, drawing on routine nursing chart data. Structural data from 16 participating LTC facilities and the care data of all residents who died in 2019 (N = 471) were collected anonymously between March and May 2020. Based on key literature on quality indicators of PC in LTC facilities in Germany, a structured survey was developed by a multidisciplinary research team. The descriptive, comparative and inferential data analysis was conducted using the SPSS software package. Results In total, the complete records of 363 (77%) residents who died in the participating LTC facilities in 2019 were retrieved. The records reflected that 45% of the residents had been hospitalized at least once during the last 6 months of their lives, and 19% had died in hospital. Advance care planning (ACP) consultation was offered to 168 (46%) residents, and 64 (38%) declined this offer. A written advance directive was available for 47% of the residents. A specialized PC team and hospice service volunteers were involved in caring for 6% and 14% of the residents, respectively. Cancer patients received support from external services significantly more frequently (p Conclusions Overall, a rather positive picture of PC in participating LTC facilities in Germany emerged, although there were differences in the expression of certain indicators between facilities. ACP consultation, volunteer hospice services, and hospital admissions appeared to be superior in LTC facilities with more trained PC staff. Therefore, PC training for staff should be further promoted.

The secondary use of deidentified but not anonymized patient data is a promising approach for enabling precision medicine and learning health care systems. In most national jurisdictions (e.g., in Europe), this type of secondary use requires patient consent. While various ethical, legal, and technical analyses have stressed the opportunities and challenges for different types of consent over the past decade, no country has yet established a national consent standard accepted by the relevant authorities.A working group of the national Medical Informatics Initiative in Germany conducted a requirements analysis and developed a GDPR-compliant broad consent standard. The development included consensus procedures within the Medical Informatics Initiative, a documented consultation process with all relevant stakeholder groups and authorities, and the ultimate submission for approval via the national data protection authorities.This paper presents the broad consent text together with a guidance document on mandatory safeguards for broad consent implementation. The mandatory safeguards comprise i) independent review of individual research projects, ii) organizational measures to protect patients from involuntary disclosure of protected information, and iii) comprehensive information for patients and public transparency. This paper further describes the key issues discussed with the relevant authorities, especially the position on additional or alternative consent approaches such as dynamic consent.Both the resulting broad consent text and the national consensus process are relevant for similar activities internationally. A key challenge of aligning consent documents with the various stakeholders was explaining and justifying the decision to use broad consent and the decision against using alternative models such as dynamic consent. Public transparency for all secondary use projects and their results emerged as a key factor in this justification. While currently largely limited to academic medicine in Germany, the first steps for extending this broad consent approach to wider areas of application, including smaller institutions and medical practices, are currently under consideration.

Single Plane Illumination Microscopy (SPIM) revolutionized time lapse imaging of live cells and organisms due to its high speed and reduced photodamage. Quantitative mapping of molecular (co)mobility by fluorescence (cross-)correlation spectroscopy (F(C)CS) in a SPIM has been introduced to reveal molecular diffusion and binding. A complementary aspect of interactions is proximity, which can be studied by Förster resonance energy transfer (FRET). Here, we extend SPIM-FCCS by alternating laser excitation, which reduces false positive cross-correlation and facilitates comapping of FRET. Thus, different aspects of interacting systems can be studied simultaneously, and molecular subpopulations can be discriminated by multiparameter analysis. After demonstrating the benefits of the method on the AP-1 transcription factor, the dimerization and DNA binding behavior of retinoic acid receptor (RAR) and retinoid X receptor (RXR) is revealed, and an extension of the molecular switch model of the nuclear receptor action is proposed. Our data imply that RAR agonist enhances RAR-RXR heterodimerization, and chromatin binding/dimerization are positively correlated. We also propose a ligand induced conformational change bringing the N-termini of RAR and RXR closer together. The RXR agonist increased homodimerization of RXR suggesting that RXR may act as an autonomous transcription factor.

ZusammenfassungEine intrauterine Wachstumsrestriktion (IUGR) betrifft Feten, die ihr intrauterines Wachstumspotenzial nicht nutzen können. Überschneidungen bestehen dabei zur Gruppe der small-for-gestational age (SGA) Kinder, doch sind speziell IUGR-Kinder von kurz- und langfristigen Folgen betroffen. IUGR-Feten haben ein deutlich erhöhtes Frühgeburtlichkeits-Risiko und ein spezielles Risikoprofil im Vergleich zu altersentsprechend gewachsenen Frühgeborenen. Dies umfasst das häufigere Auftreten typischer Komplikationen wie Bronchopulmonale Dysplasie, intraventrikuläre Hämorrhagie und Mekonium-Ileus. Neugeborene mit IUGR scheinen langfristig ein erhöhtes Risiko für Folgeprobleme, wie Zerebralparesen, eingeschränkte Lungenfunktion und Sprachentwicklungsverzögerungen zu haben. Eine transsektorale, interdisziplinäre und multiprofessionelle Betreuung der Schwangeren, Neugeborenen und Säuglinge im Rahmen eines Versorgungspfades ist eine aussichtsreiche neue Versorgungsform. Sie umfasst die frühe Identifizierung von Schwangeren mit einem erhöhten Risiko für eine fetale Wachstumsrestriktion, ggf. die Therapie mit Acetylsalicylsäure, die Risiko-adaptierte Anbindung an die Perinatalzentren mit psychologischen Interventionen und neonatologischen Gesprächen. Ziel des Pfades ist die Vermeidung von Verlegungen in die Perinatologie und Totgeburten. Postnatal steht eine umfassende Betreuung mit besonderem Augenmerk auf die Eltern-Kind-Bindung und Ernährungsoptimierung im Mittelpunkt. Vertiefende Vorsorgeuntersuchungen der ambulanten Kinderärzte dienen dem frühen Aufdecken von Entwicklungsproblemen. Die Wirkungen, Akzeptanz und Kosteneffizienz dieses Pfades werden im Rahmen eines Projektes des Innovationsfonds getestet.

As integrated care is recognized as crucial to meet the challenges of chronic conditions such as Parkinson&rsquo, s disease (PD), integrated care networks have emerged internationally and throughout Germany. One of these networks is the Parkinson Network Eastern Saxony (PANOS). PANOS aims to deliver timely and equal care to PD patients with a collaborative intersectoral structured care pathway. Additional components encompass personalized case management, an electronic health record, and communicative and educative measures. To reach an intersectoral consensus of the future collaboration in PANOS, a structured consensus process was conducted in three sequential workshops. Community-based physicians, PD specialists, therapists, scientists and representatives of regulatory authorities and statutory health insurances were asked to rate core pathway-elements and supporting technological, personal and communicative measures. For the majority of core elements/planned measures, a consensus was reached, defined as an agreement by &gt, 75% of participants. Additionally, six representatives from all partners involved in the network-design independently assessed PANOS based on the Development Model for Integrated Care (DMIC), a validated model addressing the comprehensiveness and maturity of integrated care concepts. The results show that PANOS is currently in an early maturation state but has the potential to comprehensively represent the DMIC if all planned activities are implemented successfully. Despite the favorable high level of consensus regarding the PANOS concept and despite its potential to become a balanced integrated care concept according to the DMIC, its full implementation remains a considerable challenge.

ZusammenfassungDie Verknüpfung verschiedener Datenquellen, genannt Datenlinkage oder auch Record Linkage, zur Beantwortung von wissenschaftlichen Fragestellungen findet in den letzten Jahren in Deutschland vermehrt Anwendung. Jedoch mangelt es bisher an publizierten Erfahrungen. Neue Projekte erarbeiten sich in der Regel autark voneinander das notwendige Handwerkszeug. Daher hat sich eine Gruppe von Forschern zusammengefunden, um ihre Erfahrungen zum Datenlinkage in Deutschland als mögliche Hilfestellung bzw. Anregung für Projekte, Gutachter sowie Datenschützer und Ethikkommissionen zusammenzustellen. Ziel dieser ersten Bestandsaufnahme zum Datenlinkage ist es deshalb, eine Unterstützung für zukünftige Projekte zu liefern, die Daten aus Deutschland auf individueller Ebene verknüpfen möchten. Neben den (datenschutz-)rechtlichen Rahmenbedingungen werden dabei auch praxisorientiert die Arten des Datenlinkage, deren Anwendungsfelder und Ansätze zur Vermeidung von Fehlern anhand von Beispielen dargestellt.

Diabetes self-management education (DSME) is generally considered as an integral part of diabetes care. The availability of different types of self-management in the European Union Member States (EUMS) remains uncertain. The aim of this study is to perform a comparative analysis of existing DSME programs (DSMEP) implemented in EUMS. Unpublished data regarding DSME in the EUMS was assessed with Diabetes Literacy Survey using wiki tool (WT) targeting patients and different stakeholders. An additional literature review (LR) was performed in PubMed to identify published studies regarding DSMEP in the EUMS from 2004 to 2014. A total of 102 DSMEP implemented in EUMS were reported in the WT and 154 programs were identified from the LR. Comparative analysis of the data indicated that a majority of programs are aimed at adults and only a minority at children and elderly. Only a small percentage of the programs utilize information technology for teaching and learning, and only one out of five programs pay attention to depression. The identified DSMEP aimed primarily to empower patients through increasing knowledge and changing attitudes and beliefs towards diabetes. This study provides an overview of the present state-of-the-art on diabetes self-management education programs in the 28 EUMS. To increase participation, existing DSMEP should be made more accessible to the patients as well as tailored to specific patient groups.

In Germany, no instruments exist to evaluate the practice and organisation of palliative care in general practice. The aim of this project was the systematic development and adjustment of a German version of the General Practice End of Life Care Index (GP-EoLC-I).The translation and adaptation process followed the TRAPD model: translation, review, adjudication, pre-test, documentation. The process was completed by a back translation, a first pre-test and a feasibility study with general practitioners.Nine of the ten general practitioners invited took part in the pre-test (56 % female, median age 55 years, range 40-75). The pre-test showed a median processing time of 15minutes. 17 general practitioners (59 % female, median age 53 years, range 39-69) took part in the pilot study. Adaptation to the German context was necessary for two of the 25 items. In the pre-test and in the pilot study only single values were missing. With the exception of the two adapted items, the back translation showed a high level of consistency with the original version of the questionnaire.The systematic development and testing of the questionnaire "Hausärztliche Begleitung in der letzten Lebensphase" (HA-BeL) as well as its adaptation for the primary care setting in Germany was successfully completed in a multi-stage process using an interdisciplinary and participatory approach. The results of this empirical testing provide guidance for expenditure and reasonableness, objectivity of application and content-related consistency of the HA-BeL index.The HA-BeL index is the first self-assessment instrument to be used by general practitioners to evaluate practice and organisation of palliative care in general practice in Germany.

Objectives Despite improved treatment, premature cardiovascular (CV) events remain a major health problem. Aim of this study was to evaluate the patterns of risk factors in patients with premature CV events. Methods CV risk factors (CVRF) were evaluated in 130 patients with a history of CV events (myocardial infarction, stroke, limb ischemia, stent and bypass intervention in any vessel bed) under 50 years of age attending our lipid clinic. Patients were also stratified according to their Lp(a) concentrations: group 1: 0–45 nmol/l ( 45–120 nmol/l (>18–50 mg/dl); group 3: >120 nmol/l (>50 mg/dl). Results The most common risk factors in our patients were male sex (75%), current (61%) and previous smoking (9%), arterial hypertension (70%), and a positive family history of early CV events (54%) and hyperlipidemia (69%). Only 27% had a BMI >30 kg/m2 and 14% had diabetes mellitus. 69% of patients with premature CV disease (CVD) showed Lp(a) levels > 120 nmol/l (>50 mg/dl). Patients with the highest Lp(a) showed a tendency of more frequent positive family histories of hyperlipidemia. They had experienced their first CV event on average 3 years earlier than those with low Lp(a). CV events predominantly involved coronary arteries. 85% of patients experienced at least one coronary event. Conclusion In patients with premature CV disease male sex, smoking, hypertension, a positive family history and elevated Lp(a) are the most important CV risk factors. Lp(a) should be considered in the management of young patients with CV disease.

Interleukin-2 (IL-2) and IL-15 play pivotal roles in T cell activation, apoptosis, and survival, and are implicated in leukemias and autoimmune diseases. Their heterotrimeric receptors share their β- and γ(c)-chains, but have distinct α-chains. Anti–IL-2Rα (daclizumab) therapy targeting cell surface-expressed receptor subunits to inhibit T cell proliferation has only brought limited success in adult T cell leukemia/lymphoma (ATL) and in multiple sclerosis. We asked whether IL-2R subunits could already preassemble and signal efficiently in the endoplasmic reticulum (ER) and the Golgi. A combination of daclizumab and anti–IL-2 efficiently blocked IL-2–induced proliferation of IL-2–dependent wild-type (WT) ATL cells but not cells transfected with IL-2, suggesting that in IL-2–producing cells signaling may already take place before receptors reach the cell surface. In the Golgi fraction isolated from IL-2–producing ATL cells, we detected by Western blot phosphorylated Jak1, Jak3, and a phosphotyrosine signal attributed to the γ(c)-chain, which occurred at much lower levels in the Golgi of WT ATL cells. We expressed EGFP- and mCherry-tagged receptor chains in HeLa cells to study their assembly along the secretory pathway. Confocal microscopy, Förster resonance energy transfer, and imaging fluorescence cross-correlation spectroscopy analysis revealed partial colocalization and molecular association of IL-2 (and IL-15) receptor chains in the ER/Golgi, which became more complete in the plasma membrane, further confirming our hypothesis. Our results define a paradigm of intracellular autocrine signaling and may explain resistance to antagonistic antibody therapies targeting receptors at the cell surface.

Intrauterine growth restriction (IUGR) is present in fetuses that do not achieve their full in-utero growth potential. IUGR needs to be discriminated from small for gestational age (SGA) because IUGR newborns in particular experience long-term side effects from their small growth. IUGR fetuses have a significantly increased risk of prematurity and a distinct risk profile compared to adequate-for-gestational-age preterm newborns. Complications of prematurity are more frequent, including bronchopulmonary dysplasia, intraventricular hemorrhage, and meconium ileus. IUGR newborns are at risk of long-term health issues like cerebral palsy, impaired lung function, and delayed speech development. Interdisciplinary and interprofessional care of IUGR pregnancies in the context of a standardized health care research project is feasible: Pregnant women at risk are identified, early therapy with acetylsalicylic acid is started as indicated, risk-adapted care at level III centers is organized including psychosocial interventions and neonatal consultations. Postnatally, integrated neonatal care focusing on parent-child interaction and optimized nutrition is a hallmark. Afterwards, in-depth pediatric follow-up visits with local pediatricians help to identify growth and neurodevelopment problems early. The effects, acceptance. and cost efficiency of this approach are evaluated prospectively as part of an Innovationsfonds project.Eine intrauterine Wachstumsrestriktion (IUGR) betrifft Feten, die ihr intrauterines Wachstumspotenzial nicht nutzen können. Überschneidungen bestehen dabei zur Gruppe der small-for-gestational age (SGA) Kinder, doch sind speziell IUGR-Kinder von kurz- und langfristigen Folgen betroffen. IUGR-Feten haben ein deutlich erhöhtes Frühgeburtlichkeits-Risiko und ein spezielles Risikoprofil im Vergleich zu altersentsprechend gewachsenen Frühgeborenen. Dies umfasst das häufigere Auftreten typischer Komplikationen wie Bronchopulmonale Dysplasie, intraventrikuläre Hämorrhagie und Mekonium-Ileus. Neugeborene mit IUGR scheinen langfristig ein erhöhtes Risiko für Folgeprobleme, wie Zerebralparesen, eingeschränkte Lungenfunktion und Sprachentwicklungsverzögerungen zu haben. Eine transsektorale, interdisziplinäre und multiprofessionelle Betreuung der Schwangeren, Neugeborenen und Säuglinge im Rahmen eines Versorgungspfades ist eine aussichtsreiche neue Versorgungsform. Sie umfasst die frühe Identifizierung von Schwangeren mit einem erhöhten Risiko für eine fetale Wachstumsrestriktion, ggf. die Therapie mit Acetylsalicylsäure, die Risiko-adaptierte Anbindung an die Perinatalzentren mit psychologischen Interventionen und neonatologischen Gesprächen. Ziel des Pfades ist die Vermeidung von Verlegungen in die Perinatologie und Totgeburten. Postnatal steht eine umfassende Betreuung mit besonderem Augenmerk auf die Eltern-Kind-Bindung und Ernährungsoptimierung im Mittelpunkt. Vertiefende Vorsorgeuntersuchungen der ambulanten Kinderärzte dienen dem frühen Aufdecken von Entwicklungsproblemen. Die Wirkungen, Akzeptanz und Kosteneffizienz dieses Pfades werden im Rahmen eines Projektes des Innovationsfonds getestet.

Individual data linkage of different data sources for research purposes is being increasingly used in Germany in recent years. However, generally accepted methodological guidance is missing. The aim of this article is to define such methodological standards for research projects. Another aim is to provide readers with a checklist for critical appraisal of research proposals and articles. Since 2016, an expert panel of members of different German scientific societies have worked together and developed 7 guidelines with a total of 27 practical recommendations. These recommendations include (1) research aims, questions, data sources and resources, (2) infrastructure and data flow, (3) data privacy, (4) ethics, (5) key variables and type of linkage, (6) data validation/quality assurance and (7) long-term use for future research questions. The authors provide a rationale for each recommendation. Future revisions will include any new developments in science and data privacy.Das personenbezogene Verknüpfen verschiedener Datenquellen (Datenlinkage) für Forschungszwecke findet in den letzten Jahren in Deutschland zunehmend Anwendung. Jedoch fehlen hierfür konsentierte methodische Standards. Ziel dieses Beitrages ist es, solche Standards für Forschungsvorhaben zu definieren. Eine weitere Intention ist es, dem Lesenden eine Checkliste zur Bewertung geplanter Forschungsvorhaben und Artikel bereitzustellen. Zu diesem Zweck hat eine aus Mitgliedern verschiedener Fachgesellschaften zusammengesetzte Expertengruppe seit 2016 insgesamt 7 Leitlinien mit 27 konkreten Empfehlungen erstellt. Die Gute Praxis Datenlinkage beinhaltet die folgenden Leitlinien: (1) Forschungsziele, Fragestellung, Datenquellen und Ressourcen, (2) Dateninfrastruktur und Datenfluss, (3) Datenschutz, (4) Ethik, (5) Schlüsselvariablen und Linkageverfahren, (6) Datenprüfung/Qualitätssicherung sowie (7) Langfristige Datennutzung für noch festzulegende Fragestellungen. Jede Leitlinie wird ausführlich diskutiert. Zukünftige Aktualisierungen werden wissenschaftliche und datenschutzrechtliche Entwicklungen berücksichtigen.

The change of mapping methods for seagrass beds, here species of eelgrasses, from aerial surveys to automated classification of optical satellite data is described. Both methods are compared with respect to availability and suitability of their data. Differences in the detection capability of the methods are shown as well as results of the validation of the satellite image classification. In North Friesia, where the largest area of eelgrass occurs in the Wadden Sea, eelgrass beds have been mapped regularly using aerial surveys since 1994. After a significant decline in the 1930s and 1960s, monitoring results show a steady increase in the size of the area covered by eelgrass beds up to 2017. Since 2006, the aerial surveys have been complemented by ground surveys, which, however, only cover one sixth of the area of the Schleswig-Holstein Wadden Sea each year. Results show that size estimates of individual beds can vary significantly between aerial and ground surveys. In recent years, satellite-borne remote sensing technology and subsequent analysis methods have reached a level of quality, which makes them an alternative and cost-efficient method for mapping eelgrass. The technology has advantages such as the coverage of large areas at single points in time, repeatable and transferable image analysis methods, and high spatial resolution of the satellite images, as well as frequent repetition of acquisition of data. This provides standardised results, which allow direct comparisons over time and between areas.