15,757 research outputs found

    Regionale Versicherungsrisiken unter dem morbiditätsorientierten Risikostrukturausgleich: Detektion, Ursachen und Reformbedarf der Wettbewerbsbedingungen in der GKV

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    Der Risikostrukturausgleich (RSA) ist der finanzielle Ausgleichsmechanismus zwischen den Krankenkassen. Er beschreibt, wie die Gelder des Gesundheitsfonds, dem Risiko gerecht, zwischen den Krankenkassen zu verteilen sind. Es ist das vordergründige Ziel des RSA die Möglichkeit der Selektion von guten und schlechten Risiken (Risikoselektion) durch die Krankenkassen zu verhindern. Ohne einen RSA sind neben einem Verstoß gegen das Solidaritätsprinzip (BVerfG, Rn. 162 (18.07.2005)) Effizienzverluste durch die Verschiebung des Wettbewerbes zwischen den Krankenkassen von Qualität auf Risikoselektion (z.B. die Attrahierung von jungen und gesunden Personen), zu befürchten. Die These, die in dieser kumulativen Dissertation untersucht wird, ist, dass das Merkmal der regionalen Herkunft der Versicherten geeignet ist, um gute Risiken von schlechten Risiken zu trennen und somit Anreize zur Risikoselektion bietet. Es wird argumentiert, dass die räumliche Autokorrelation von individuellen Deckungsbeiträgen ein geeignetes Maß ist, um Anreize zur regionalen Risikoselektion zu erkennen. Dabei steht das Argument im Vordergrund, dass neben absoluten Deckungsbeitragsunterschieden die Validität der Information „regionale Herkunft“ für Risikoselektion entscheidend ist. Die zweite Fragestellung der Dissertation betrifft die Ursachen der regionalen Risiken für Krankenkassen. Die Identifikation von Ursachen verfolgt dabei das Ziel zu begründen, ob die Versicherungsrisiken, die mit der regionalen Herkunft assoziiert sind, gemäß des Solidaritätsprinzips durch die Gesamtheit der Versichertengemeinschaft zu tragen wären. Drittens wird die geographisch gewichtete Regression auf die Aspekte des Risikostrukturausgleichs angepasst und ein Verfahren beschrieben, wie die Regression auf dem sehr umfangreichen Datensatz des RSA effizient umgesetzt werden kann. Nach einer langen Debatte unter Gesundheitsökonomen wurde für das Ausgleichsjahr 2021 erstmals eine Regionalisierung im RSA vorgenommen. Den Einzelveröffentlichungen dieser Dissertation war es beschieden, am gesundheitsökonomischen Diskurs teilzuhaben und letztlich die Einführung der Regionalisierung im RSA begleitet zu haben.:1 Einleitung 1.1 Solidarität und Wettbewerb in der GKV 1.2 Motivation der Arbeit und Einordnung in die Literatur 1.3 Forschungsfragen und Gang der Arbeit 2 Der Einfluss der Regionalität auf den Versicherungswettbewerb 2.1 Der wettbewerbliche Ordnungsrahmen der GKV 2.2 Dysfunktionale Folgen eines regional unvollständigen RSA 2.3 Maßzahlen der wettbewerblichen Neutralität des 3 Räumliche Versicherungsrisiken im solidarischen Wettbewerb 3.1 Solidarität im RSA 3.2 Ursachen für regionale Risiken 3.3 Einnahmerisiko 3.4 Mengen- und Strukturrisiko 3.5 Preisrisiko 4 Abbildung von räumlichen Versicherungsrisiken im RSA 4.1 Die Funktionsweise des RSA zwischen 2009 und 2020 4.2 Das M2-Modell 4.3 Das GWR-Modell 4.4 Ein empirischer Vergleich der Regionalisierungsansätze 5 Fazi

    Long-acting reversible contraception (LARC) after pregnancy and childbirth

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    Background and aims: Unmet need of contraception is a global challenge. The need of additional visits to initiate contraception is found to be a barrier for postpartum and postabortion contraceptive care. The IUDs and the implant are called long-acting reversible contraception (LARC). The LARC-method can be used for years without having to remember a contraceptive during sexual intercourse or, in case of hormonal contraception, every day, week or month. The overall aim of this thesis was to add knowledge to the field of long-acting reversible contraception after pregnancy in Sweden in our effort to improve the quality of contraceptive care after pregnancy and childbirth. Methods and main results: Study 1 was a retrospective cohort study including 11,066 women. Data was extracted from medical records regarding attendance to the postpartum visit and choice of contraception, breastfeeding, and abortion during 12-24 months after delivery. The primary outcome was the proportion of induced abortions during follow-up, with the outcome measure of abortion being a surrogate for unintended pregnancy. Among attendees to the follow up 2.1 % had an abortion compared to 3.6 % among nonattendants. A decision to use LARC was associated with a lower risk of abortion (OR 0.74; 95% CI 0.60-0.91; p = .005), as was exclusive breastfeeding (p < .001). Smoking and having had an earlier abortion were associated with a higher risk of abortion during the follow-up. Study II and III were open-label, prospective, randomised, controlled, multicenter studies. In study II, 101 women were either allocated to early placement (52/101) of a hormonal IUD within 48 hours after vaginal delivery or to standard placement (49/101) at 6-8 weeks postpartum. Follow-up was one year after IUD placement. Inclusion was prematurely stopped after an interim analysis due to high expulsion rate in the early placement group, and instead of 600 women only 101 were included. In the early placement group 23/52 (44.2 %) of devices were expelled within a year and 10 women had the hormonal device replaced. In the standard placement group there were no expulsions. The IUD continuation rate for the early group was 37/52 (71.2%), compared to 41/49 (83.7%, p = .13) for the standard placement group at study closure. In study III, 240 women seeking medical abortion up to 63 days´ gestation were randomised to either IUD placement within 48 hours (120/240) after completed abortion or to IUD placement at 2-4 weeks (120/240) after abortion. Follow-up was one year after abortion. The primary outcome was IUD use at 6 months postabortion. In the early placement group (intervention), 91/111 (82%) women used IUD at 6 months compared to 87/112 (77.7%) in the later placement (control) group (p= .51) Pain scores at IUD placement (measured by the visual analogue scale) were lower in the intervention group (p= .002). Women in the intervention group preferred the allocated time significantly more often compared to the control group (p= .03). There was no difference regarding expulsion. In study II and III there were no differences regarding safety profile between groups. Study IV was a qualitative study where 20 women who had undergone elective caesarean section (CS) were interviewed within 6 weeks of CS, to enable deeper understanding of women´s preferences and needs regarding contraceptive services at the time of pregnancy. Ten of the interviewees had chosen IUD placement during the latest CS. Three themes were identified; Receptivity to contraceptive counseling during pregnancy; Communication and decision-making of postpartum contraception during pregnancy and Needs to navigate in the Maternal Health Care System to receive contraceptive services before and after caesarean section. Women were generally positive to contraceptive counseling from about 25 gestational weeks and expressed positive attitudes about the concept of antenatal counseling. Feeling involved and informed was important, but few women had been involved in antenatal counseling. Women who had chosen IUD placement during CS were usually satisfied with the decision. Some interviewees expressed a need to navigate in the contraceptive services by themselves. The communication and coordinating units that should integrate around the woman have not sufficiently adapted to new evidence, needs and conditions. Conclusions: The choice of LARC postpartum is associated with lower risk for unintended pregnancy compared to the choice of other contraceptives or no choice at all. Attendance to the postpartum visit is a prerequisite to initiate LARC when provision of early/immediate LARC initiation postpartum is not part of the established contraceptive health care. Placement of a hormonal IUD within 48 hours after vaginal delivery seems safe, accepted by patients but associated with much higher expulsion rates compared to placement 6- 12 weeks postpartum. Early placement of an IUD within 48 hours after completed medical abortion does not lead to higher continuation rates at one year after abortion compared to standard placement 2-4 weeks after abortion when devices are provided free of charge. Early placement seems safe, preferred by patients, and associated with lower pain scores compared to standard IUD placement postabortion. Antenatal counseling for contraceptive method to use postpartum seems acceptable to women from around 25 gestational weeks. To have the opportunity to discuss contraception antenatally and enable placement during planned CS is generally considered valuable

    Complement mediated synapse elimination in schizophrenia

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    Schizophrenia (SCZ) is a devastating psychiatric disorder with a typically age of onset in late adolescence. The heritability is estimated to be in between 60-80% and large-scale genome-wide studies have revealed a prominent polygenic component to SCZ risk and identified more than three-hundred common risk variants. Despite a better understanding of which genetic risk variants that increases SCZ risk, it has been challenging to map out the pathophysiology of the disorder. This has stalled the development of target drugs and current treatment options display moderate efficacy and are prone to produce side-effects. SCZ is generally considered a neurodevelopmental disorder and it was proposed more than forty years ago that physiological removal of less active synapses in adolescence, i.e., synaptic pruning, is increased in SCZ and hereby causes the core symptoms of the disorder. This theory has then been supported by post-mortem brain tissue and imaging studies displaying decreased synapse density in SCZ. More recently, it was then shown that the most strongly associated risk loci can largely be explained by copy numbers of a gene coding for the complement factor 4A (C4A). As microglia prune synapses with the help of complement signalling, we therefore decided to use a recently developed human 2D in vitro assay to assess microglial uptake of synaptic structures in models based on cells from individuals with SCZ and healthy controls (study I). We observed excessive uptake of synaptic structures in SCZ models and by mixing synapses from healthy controls with microglia from SCZ patients, and vice versa, we showed the contribution of microglial and neuronal factors contributing to this excessive uptake of synaptic structures. We then developed an in vitro assay to study neuronal complement deposition dependent on copy numbers of C4A in the neuronal lines. Complement 3 (C3) deposition increased by C4A copy numbers but was independent of C4B copy numbers (also unrelated to SCZ risk). Similar C4A copy numbers correlated with the extent of microglial uptake of synapses. Microglial uptake of synaptic structures could also be inhibited by the tetracycline minocycline that also decreased risk of developing SCZ in an electronic health record cohort. In study II, we cerebrospinal fluid (CSF) from first-episode psychosis patients to measure protein levels of C4A. In two independent cohorts, we observed elevated C4A levels (although not C4B levels) in first-episode patients that later were to develop SCZ and could show correlations with markers of synapse density. However, elevated C4A levels could not fully be explained by more copy numbers of C4A in individuals with SCZ and in vitro experiments revealed that SCZ-associated cytokines can induce C4A mRNA expression while also correlating with C4A in patient-derived CSF. In study III, we set-up a 3D brain organoid models to more fully comprehensively capture processes in the developing human brain and then also included innately developing microglia. We display synaptic pruning within these models and use single cell RNA sequencing to validate them. In conclusion, this thesis uses patient-derived cellular modelling to uncover a disease mechanism in SCZ that link genetic risk variants with bona fide protein changes in living patients

    Nutrition and cognitive health: A life course approach

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    Multiple factors affect cognitive health, such as age-related changes in the brain, injuries, mood disorders, substance abuse, and diseases. While some cannot be changed, evidence exists of many potentially possibly modifiable lifestyle factors: diet, physical activity, cognitive and social engagement, smoking and alcohol consumption which may stabilize or improve declining cognitive function. In nutrition, the focus has been mainly on its role in brain development in the early years. There is a strong emerging need to identify the role of diet and nutrition factors on age-related cognitive decline, which will open up the use of new approaches for prevention, treatment or management of age-related disorders and maintaining a good quality of life among older adults. While data on effect of high protein diets is not consistent, low-fat diets are protective against cognitive decline. Several micronutrients like B group vitamins and iron, as well as many polyphenols play a crucial role in cognitive health. Mediterranean, Nordic, DASH, and MIND diets are linked to a lower risk of cognitive decline and dementia. The relationship between the gut microbiome and brain function through the gut-brain axis has led to the emergence of data on the beneficial effects of dietary fibers and probiotics through the management of gut microbes. A “whole diet” approach as well as macro- and micro-nutrient intake levels that have protective effects against cardiovascular diseases are most likely to be effective against neurodegenerative disorders too. Young adulthood and middle age are crucial periods for determining cognitive health in old age. The importance of cardio metabolic risk factors such as obesity and hypertension, smoking and physical inactivity that develop in middle age suggest that preventive approaches are required for target populations in their 40s and 50s, much before they develop dementia. The commonality of dementia risk with cardiovascular and diabetes risk suggests that dementia could be added to present non-communicable disease management programs in primary healthcare and broader public health programs

    China’s approach to international law and the Belt and Road Initiative - perspectives from international investment law

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    This dissertation examines China’s approach to international law. In order to do so, it compares the country’s stance on international dispute resolution in past and present times. After a first historical chapter outlining China’s changeable relationship with international adjudication, the thesis subsequently focuses on contemporary developments. The emphasis here is on international instruments and mechanisms that China uses to protect investments within the Belt and Road Initiative. This dissertation combines doctrinal analysis with concrete case studies and applies deductive as well as inductive methods. The study of the legal dimension of the initiative leads to the basic assumption that two coexisting regulatory complexes provide investment protection within the initiative. Accordingly, as a first complex, the dissertation analyses China’s design of investment protection treaties and China’s stance in the reform debate on the future of in-vestment arbitration. As an outcome, the analysis claims that even though the first complex does not relate specifically to the Belt and Road Initiative, this complex nevertheless has inextricable links to China’s approach in the initiative’s context. Soft law documents, which China has concluded with both state and non-state actors, and informal mechanisms of dispute resolution form the second regulatory complex. The study investigates their functions for investment protection in the Belt and Road Initiative. In an overall view of the two regulatory complexes, this dissertation finds that China uses strictly legal and rather political methods for investment protection. In the synopsis of this result with the findings obtained from the historical part, the study concludes that China follows a realist approach to international law

    A Ghostly Closure? The Strange History of Brinkley Female College, Nineteenth-Century Spiritualism, and the Terminal Effects of Sensationalist Journalism

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    In 1871, Brinkley Female College in Memphis, Tennessee, closed due to a ghost story, regional interest in Spiritualism, and sensationalist journalism that harmed the short-lived academy. Spiritualism—a religio-spiritual movement punctuated by medium-guided communications between the living and deceased—was well-followed, though often contested during the nineteenth century. Spiritualism grew in popularity in the American South due to mass deaths resulting from yearly epidemics and the American Civil War. At the same time, sensationalist print media was widespread, and newspaper firms profited from unchecked accounts of Spiritualist seances and supernatural encounters. In the midst of this, higher education had expanded across the state of Tennessee. In the early years of Memphis-based women’s higher education, newspapers stoked interest in the paranormal by publishing unverified events attributed to a local women’s college. Sensationalist, penny-dreadful newspaper accounts influenced public perceptions, caused enrollment decline at Brinkley Female College, and resulted in institutional closure. As such, this case study recounts an unusual catalytic moment within the context of heightened Spiritualistic belief and uncouth journalistic practices. Ultimately, this study seeks to detail the influence of regional religious practices and sensational journalism on institutional termination

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
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