An exclusive human milk diet for very low birth weight newborns—A cost-effectiveness and EVPI study for Germany

Scholz S, Greiner W. An exclusive human milk diet for very low birth weight newborns—A cost-effectiveness and EVPI study for Germany. PLOS ONE. 2019;14(12): e0226496.Objectives Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow’s milk-based fortifiers in very low birth weight newborns. Methods A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values. Results In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent. Conclusion Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany

Lattice simulations with Nf=2+1N_f=2+1 improved Wilson fermions at a fixed strange quark mass

The explicit breaking of chiral symmetry of the Wilson fermion action results in additive quark mass renormalization. Moreover, flavour singlet and non-singlet scalar currents acquire different renormalization constants with respect to continuum regularization schemes. This complicates keeping the renormalized strange quark mass fixed when varying the light quark mass in simulations with $N_f=2+1$ sea quark flavours. Here we present and validate our strategy within the CLS (Coordinated Lattice Simulations) effort to achieve this in simulations with non-perturbatively order-$a$ improved Wilson fermions. We also determine various combinations of renormalization constants and improvement coefficients.Comment: 18 pages, 11 Figures, V2: References added/updated, all fits rerun with improved statistics for ensemble N204, also using the final values for the improvement coefficients A and b_P-b_A (very minor impact), The figures have been replotted accordingly. (The differences with respect to V1 are invisible to the human eye). Minor change

Migration-Led Institutional Change in Urban Development and Planning (Editorial)

The migration-city-nexus has become central in migration and urban studies alike. This ‘local turn’ has not only initiated a rethinking of the local level as an independent level of migration policy-making but also broadened the discourse on how migration processes actually change cities. Therefore, the thematic issue at hand seeks to understand how migration-led development processes in cities promote and shape institutional change, and which actors transform policies, structures, and discourses on migration in different settings. It questions how migration-related issues in urban development are being handled and transformed by local state and civil society actors. With 11 empirical articles on local negotiations of migration in urban development in different settings, this thematic issue applies an institutional change perspective on local migration policy-making to contribute to a broader understanding of migration-led development in both urban and migration studies. When it comes to clearly capturing migration-led institutional change in urban development and planning, the contributions demonstrate great heterogeneity. They reveal that research on migration-led institutional change still has many biases and is very dependent on theoretical perspectives, positionalities of researchers, and the local context of the case studies

Modell zur datenbankgestützten Planung automatisierter Montageanlagen

Die Entwicklung rechnergestützter Planungswerkzeuge für die Montage ist für die gegenwärtigen Automatisierungsbestrebungen in der Montage von grundlegender Bedeutung. Die vorliegende Arbeit verfolgte eine dreifache Zielsetzung. Eine systemtechnische Betrachtung der Montage sollte dazu dienen, das Wissen über an der Montage beteiligte Komponenten zu systematisieren und zu klassifizieren. Es sollte zusätzlich ein Beitrag geleistet werden, bestehende Lücken in der Planungssystematik für die Montage zu schließen. Ein besonderes Anliegen war es, zu zeigen, wie Datenbanken entworfen werden können, mit denen einzelne Planungswerkzeuge zu einem Gesamtsystem integriert und damit effektiver genutzt werden können. Zunächst wurden die entsprechenden Aufgabenstellungen in Kapitel 2 kurz vorgestellt und gezeigt, daß dem Einsatz von Datenbanken in einer Verfahrenskette zur Montageplanung eine zentrale Bedeutung zukommt. Bisher wurden Datenbanken im Bereich der Montageplanung jedoch kaum genutzt. Dies wird hauptsächlich darauf zurückgeführt, daß die vorwiegend für kommerzielle Anwendungen entwickelten Datenbankmanagementsysteme für technische Anwendungen nur unzureichend geeignet sind und der Datenbankentwurf sich als eine sehr komplexe Aufgabenstellung darstellt. Kapitel 3 enthält eine Einführung in die Begriffswelt der Datenbanktechnologie. Besonderer Wert wurde auf die Darstellung der Methoden zum Datenbankentwurf gelegt. Es wurde der Weg von der Bedarfsanalyse bis zum implementierfähigen konzeptionellen Schema aufgezeigt. Eine systemtechnische Betrachtung der Montage wurde in Kapitel 4 durchgeführt. Die Montage wurde dazu auf ein soziotechnologisches Modell abgebildet, welches eine klare Abgrenzung der einzelnen an der Montage beteiligten Komponenten ermöglicht. Die Ergebnisse dieser Systemanalyse dokumentieren, daß die Systemtechnik ein unerläßliches Hilfsmittel darstellt, um zu einer strukturierten Beschreibung eines so komplexen Problemkreises, wie ihn die Montage darstellt, zu gelangen. In Kapitel 5 wurde der Ablauf der systematischen Montageanlagenplanung analysiert. Um die Lücke in der systematischen Montageplanung zwischen der Beschreibung der Montageaufgabe und der Erstellung des Montagelayouts zu schließen, wurde ein neues Verfahren zur Montageablaufbeschreibung entwickelt. Dieses Verfahren zeichnet sich dadurch aus, daß anhand einer operationalen Beschreibung des Montageablaufs direkt, geeignete Wirkorgane und Geräte zur Durchführung der Montage, aus einer Datenbasis ausgewählt werden können. Diese beiden Kapitel bildeten die Grundlage für die Entwicklung eines konzeptionellen Schemas, mit dem der gesamte Ablauf der Montageplanung, wie er in Kapitel 5 dargestellt wurde, unterstützt werden kann. Es wurden zunächst semantische Schemata für die einzelnen Planungsschritte entworfen und diese dann zu einem gemeinsamen konzeptionellen Schema integriert. Zum Abschluß der Arbeit wurden die Implementierung einer Datenbank nach diesem konzeptionellen Schema und exemplarische Realisierungen von Anwenderprogrammen, die mit dieser Datenbank arbeiten, vorgestellt. Die Arbeit hat gezeigt, daß schon durch die für die Vorbereitung eines Datenbankeinsatzes erforderliche systematische Betrachtung der Montage wesentliche Erkenntnisse zur Montageplanung gewonnen werden können. Zudem kann auch mit derzeit verfügbaren Datenbankmanagementsystemen, trotz der in Kapitel 3 angesprochenen Unzulänglichkeiten, eine wirkungsvolle Unterstützung der rechnergestützten Montageplanung erreicht werden, indem der Eingabeaufwand für einzelne Anwendungsprogramme erheblich reduziert und Fehler durch redundante Datenspeicherung weitgehend vermieden werden.The development of computer-aided planning tools for assembly is of fundamental importance for the current automation efforts in assembly. The present work pursued a threefold objective. A systematic view of the assembly should serve to systematize and classify the knowledge about components involved in the assembly. An additional contribution should be made to close existing gaps in the planning system for assembly. A particular concern was to show how databases can be designed, with which individual planning tools can be integrated into an overall system and thus used more effectively. First, the corresponding tasks were briefly presented in Chapter 2 and it was shown that the use of databases in a process chain for assembly planning is of central importance. So far, databases in the area of assembly planning have hardly been used. This is mainly attributed to the fact that the database management systems, which were developed primarily for commercial applications, are insufficiently suitable for technical applications and the database design presents itself as a very complex task. Chapter 3 introduces the conceptual world of database technology. Particular emphasis was placed on the presentation of the methods for database design. The path from the needs analysis to the implementable conceptual scheme was shown. A system-technical examination of the assembly was carried out in chapter 4. For this purpose, the assembly was mapped onto a socio-technological model, which enables a clear demarcation of the individual components involved in the assembly. The results of this system analysis document that the system technology is an indispensable aid in order to arrive at a structured description of such a complex problem as the assembly represents. In Chapter 5, the process of systematic assembly system planning was analyzed. In order to close the gap in the systematic assembly planning between the description of the assembly task and the creation of the assembly layout, a new procedure for the assembly process description was developed. This method is characterized in that, based on an operational description of the assembly process, suitable active elements and devices for carrying out the assembly can be selected directly from a database. These two chapters formed the basis for the development of a conceptual scheme that can be used to support the entire assembly planning process, as described in Chapter 5. First, semantic schemes for the individual planning steps were designed and then integrated into a common conceptual scheme. At the end of the work, the implementation of a database according to this conceptual scheme and exemplary implementations of user programs that work with this database were presented. The work has shown that the systematic consideration of assembly required for the preparation of a database deployment can provide essential insights into assembly planning. In addition, with the currently available database management systems, despite the shortcomings mentioned in Chapter 3, effective support for computer-aided assembly planning can be achieved by considerably reducing the input effort for individual application programs and largely avoiding errors due to redundant data storage

The Normal Fetal Heart Rate Study: Analysis Plan

Recording of fetal heart rate via CTG monitoring has been routinely performed as an important part of antenatal and subpartum care for several decades. The current guidelines of the FIGO (ref1) recommend a normal range of the fetal heart rate from 110 to 150 bpm. However, there is no agreement in the medical community whether this is the correct range (ref2). We aim to address this question by computerized analysis (ref 3) of a high quality database (HQDb, ref 4) of about one billion electronically registered fetal heart rate measurements from about 10,000 pregnancies in three medical centres over seven years. In the present paper, we lay out a detailed analysis plan for this evidence-based project in the vein of the validation policy of the Sylvia Lawry Centre for Multiple Sclerosis Research (ref 5) with a split of the database into an exploratory part and a part reserved for validation. We will perform the analysis and the validation after publication of this plan in order to reduce the probability of publishing false positive research findings (ref 6-7)

Epidemiology and cost of seasonal influenza in Germany - a claims data analysis

Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age.Peer Reviewe

Induced pluripotent stem cell-derived brain organoids as potential human model system for chemotherapy induced CNS toxicity

Neurotoxic phenomena are among the most common side effects of cytotoxic agents. The development of chemotherapy-induced polyneuropathy (CIPN) is a well-recognized adverse reaction in the peripheral nervous system, while changes of cognitive functions (post-chemotherapy cognitive impairment (PCCI)) are more diffuse and have only recently drawn scientific interest. PCCI in patients most often displays as short-term memory loss, reduced multitasking ability or deficits in language. Not least, due to a lack of preclinical human model systems, the underlying molecular mechanisms are poorly understood, and treatments are missing. We thus investigated whether induced pluripotent stem cell (iPSC)-derived brain organoids can serve as a human model system for the study of chemotherapy induced central nervous system toxicity. We robustly generated mature brain organoids from iPSC-derived neuronal precursor cells (NPC), which showed a typical composition with 1) dividing NPCs forming ventricle like structures 2) matured neurons and 3) supporting glial cells closer to the surface. Furthermore, upon stimulation the brain organoids showed functional signaling. When exposed to increasing concentrations of paclitaxel, a frequently used chemotherapy drug, we observed time dependent neurotoxicity with an EC50 of 153 nM, comparable to a published murine model system. Histological analysis after paclitaxel exposure demonstrated dose dependent apoptosis induction and reduced proliferation in the organoids with further Western blot analyses indicating the degradation of neuronal calcium sensor one protein (NCS-1) and activation of Caspase-3. We could also provide evidence that paclitaxel treatment negatively affects the pool of neuronal and astrocyte precursor cells as well as mature neurons. In summary our data suggests that human iPSC derived brain organoids are a promising preclinical model system to investigate molecular mechanisms underlying PCCI and to develop novel prevention and treatment strategies.Peer Reviewe