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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Medizinische Informatik, Biometrie und Epidemiologie; VOL: 8; DOC02 /20120926/
    Publication Date: 2012-09-28
    Description: Background: A small group of patients accounts for a high amount of health care expenditures in Germany as well as in other countries. A portion of these expenses could be prevented by early identification of potential high users. This is possible through predictive modelling which offers various of methodical approaches. Therefore, the aim of this study is to identify different methodological approaches of predictive modelling of potential high users and to aid the decision-making process for the selection of appropriate method.Method: A systematic literature search was done in the scientific database SciVerse Scopus in October 2011 and supplemented by a manual search. Two persons selected identified citations in a two-step procedure independently, according to predetermined inclusion and exclusion criteria.Results: From the 216 identified publications, 18 articles remained after the final selection process. Two different approaches for dealing with this topic can be identified. On the one hand, there is an approach that focuses on patient-characteristics. Therefore, studies using this approach define high cost patients based on the frequency of health care utilization. The methods used for this approach are logistic, linear and negative binomial regression, with logistic regression as the most common one. On the other hand, there is a cost-oriented approach. Papers with this focus are primarily interested in testing different methods and new ways of prediction. The common method of logistic regression is used as well as the very special method of extreme regression. Data-mining techniques and classification systems like diagnostic cost groups are utilized as well. These methods are suitable for preparation and information processing of a large amount of diagnostic data. Conclusion: Different methods to predict high users exist. The choice of the method depends on the research question, the aim, the data and the available resources. When research focuses on predictors of high usage, logistic regression is a suitable and commonly used method.
    Description: Hintergrund: Auf einen kleinen Anteil von Patienten entfällt ein großer Anteil der Krankheitsausgaben. Dies zeigen sowohl deutsche als auch internationale Studien. Ein Teil dieser Ausgaben könnte durch frühzeitige Identifikation potentieller Hochnutzer vermieden werden. Dies ist unter anderem durch die Entwicklung eines Prädiktionsmodells möglich, wobei die methodische Umsetzung eines solchen Modells sehr unterschiedlich aussehen kann. Ziel dieser Arbeit ist deshalb herauszuarbeiten, welche methodischen Möglichkeiten es gibt, um ein Prädiktionsmodell zu erstellen, mit dem man frühzeitig steuerbare Hochnutzer finden kann, und daraus eine Entscheidungshilfe für die Wahl einer Methode abzuleiten.Methode: Es wird eine systematische Suchrecherche in der Literaturdatenbank SciVerse Scopus im Oktober 2011 durchgeführt und durch Handrecherche ergänzt. Die Literatur wird in einem zweistufigen Vieraugenverfahren nach vorher definierten Ein- und Ausschlusskriterien selektiert. Ergebnisse: Von 216 identifizierten Publikationen werden abschließend 18 in die Analysen eingeschlossen. Diese Artikel können in zwei Gruppen unterteilt werden. Auf der einen Seite gibt es Ansätze, bei denen Patienten-Charakteristika im Vordergrund stehen und die Hochnutzer über ihre Inanspruchnahmehäufigkeit von Gesundheitsleistungen definieren. Dabei kommen die Methoden der logistischen, linearen und negativ binomialen Regression zum Einsatz, wobei die logistische die am häufigsten verwendete Methode darstellt. Auf der anderen Seite gibt es kostenorientierte Ansätze. Bei Artikeln mit einem Fokus auf Kosten stehen häufig methodische Aspekte und die Möglichkeiten der Prädiktion im Vordergrund. Die Methode der logistischen Regression kommt ebenso zum Einsatz wie die sehr spezielle Form der "Extreme Regression". Außerdem gibt es mit dem Einsatz von Data-mining Techniken sowie mit Klassifikationssystemen - wie "Diagnostic Cost Groups" - Ansätze, die auf die Aufbereitung und Informationsverarbeitung großer Mengen von Diagnoseinformationen ausgelegt sind.Schlussfolgerung: Es gibt verschiedene Methoden zur Prädiktion von Hochnutzern. Die Wahl der Methode sollte sich nach der Fragestellung und dem Ziel, der Datenbasis sowie den verfügbaren Ressourcen richten. Bei Ansätzen, bei denen die Wahl geeigneter Prädiktoren im Vordergrund steht, stellt die logistische Regression eine geeignete und häufig verwendete Methode dar.
    Keywords: frequent attenders ; high-cost cases ; heavy user ; predictive modelling ; methods ; Hochnutzer ; Hochkostenfälle ; Prädiktion ; Prädiktionsmodell ; Methoden ; ddc: 610
    Language: German
    Type: article
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  • 3
    Keywords: GROWTH ; IRRADIATION ; radiotherapy ; carcinoma ; THERAPY ; DEPENDENCE ; ACCELERATED ELECTRONS ; FADU
    Abstract: The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.
    Type of Publication: Journal article published
    PubMed ID: 25600561
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  • 4
    Abstract: BACKGROUND: Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin-glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model. MATERIALS AND METHODS: Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re-suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N- and G-ratios. Additionally, muscle weight quotient (operated vs. non-operated site of the same animal) was calculated and compared between treatment and control groups. For co-detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM-DiI, SMA, and S-100 antibodies, respectively. RESULTS: ADSCs led to a significant increase of myelinization at day 21 (0.508 +/- 0.085 mum vs. 0.381 +/- 0.044 mum, P = 0.025) and day 35 (0.872 +/- 0.09 microm vs. 0.495 +/- 0.078 microm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 +/- 119 vs. 129 +/- 63; P = 0.003) and day 63 (284 +/- 137 vs. 111 +/- 26; P = 0.046) after surgery. N- and G-ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P 〈 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% +/- 6.16% vs. 35.03% +/- 2.61%; P = 0.014) and day 63 (65.49% +/- 2.81% vs. 58.79% +/- 4.06%; P = 0.009) after surgery. Co-detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis. CONCLUSION: ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:491-500, 2016.
    Type of Publication: Journal article published
    PubMed ID: 26716599
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC); 20150607-20150610; Karlsruhe; DOCDI.25.03 /20150602/
    Publication Date: 2015-06-03
    Keywords: SAH ; neuroprotection ; endothelin ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    Keywords: ANGIOGENESIS ; MRI ; TRANSPORT ; NEUROPROTECTION ; CHANNELS ; neurotoxicity
    Abstract: BACKGROUND AND PURPOSE: To evaluate the short-term outcome of erythropoietin (EPO) therapy in rats with spinal cord injury (SCI) using manganese-enhanced magnetic resonance imaging (MEMRI). METHODS: Rats were divided in an EPO and a control group. Laminectomy at Th11 was performed, followed by SCI. MnCl2 was applied into the cisterna magna and functional recovery was examined after injury using BBB-scoring. Then, rats were euthanized and the spinal cord was extracted for MEMRI. Finally, histological analysis was performed and correlated with MEMRI. RESULTS: EPO-treated animals showed significantly better functional recovery (P = .008, r = .62) and higher mean signal-to-noise ratio (SNR) in MEMRI compared to controls for slices 10-13 (P = .017, R(2) = .31) at the level of the lesion epicenter. Functional recovery correlated significantly with higher SNR values, determined using the mean SNR between slices 10 and 13 (P = .047, R(2) = .36). In this region, histology revealed a significantly decreased number of microglia cells and apoptosis in EPO-treated animals. CONCLUSION: MEMRI successfully depicts the therapeutic effect of EPO in early SCI that leads to a significant recovery in rats, a significantly reduced immune response and significantly reduced number of apoptotic cells at the height of the lesion epicenter.
    Type of Publication: Journal article published
    PubMed ID: 25510176
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  • 7
    Abstract: Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers. We further demonstrate that decreased Treg distribution in the BM correlated with increased Treg redistribution to tumor tissue, suggesting that TCR triggering induces a translocation of Treg from the BM into tumor tissue. Sphingosine-1-phosphate receptor 1 (S1P1)-which is known to mediate exit of immune cells from lymphoid organs was selectively expressed by tumor antigen-specific BM Treg. S1P1 expression could be induced in Treg by BM-resident antigen-presenting cells (BMAPCs) in conjunction with TCR stimulation, but not by TCR stimulation or BMAPCs alone and triggered the migration of Treg but not conventional T cells (Tcon) to its ligand Sphingosine-1-phosphate (S1P). Interestingly, we detected marked S1P gradients between PB and BM in breast cancer patients but not in healthy individuals. Taken together, our data suggest a role for S1P1 in mediating the selective mobilization of tumor specific Treg from the BM of breast cancer patients and their translocation into tumor tissue.
    Type of Publication: Journal article published
    PubMed ID: 28224210
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  • 8
    Abstract: Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. More than 200 CAR T cell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.
    Type of Publication: Journal article published
    PubMed ID: 28765140
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  • 9
    Abstract: The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.
    Type of Publication: Journal article published
    PubMed ID: 29786085
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  • 10
    Keywords: RECEPTORS ; GLUCOCORTICOID-RECEPTOR ; STRESS ; RECEPTOR ; Germany ; CHRONIC SOCIAL STRESS ; regulation ; pharmacology ; GLUCOCORTICOID-RECEPTORS
    Type of Publication: Meeting abstract published
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