[Limits of the G-DRG system to reflect Complexity in German University Hospitals]. / Die Grenzen des G-DRG-Systems bei der Abbildung von Komplexität in der Universitätsmedizin.

Since the introduction of the G-DRG-system in Germany for the reimbursement of in-hospital patients in 2003 the Institute for the Hospital Remuneration System (InEK) annually determines case reimbursements for currently 1300 individual diagnosis-related groups (DRGs). These are based on the cost documentation of 200 representative hospitals, coopted by InEK (§â€Š21-KHEntG-dataset). Since DRGs represent cost averages, one half of German hospitals would be expected to report an annual income surplus, the other half a deficit. In spite of sustained cost reductions two thirds of public University Hospitals, but only 29 % of non-University hospitals, report annual deficits. The German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) has obtained the §â€Š21-cost-dataset from 74 InEK-hospitals and 7 Mio anonymized cases since 2012 in order to appeal for individual DRG-corrections to InEK. In the current project this database was used to investigate whether the cost of care at University Hospitals is appropriately reflected in three representative DRGs and OPS codes (operation and procedure codes): Liver cirrhosis with hepatic encephalopathy, endoscopic procedure-tiers, and an endoscopic intervention after patient transfer from one hospital to another. The analysis reveals that the higher patient complexity, severity and cost at University Hospitals cannot be corrected by modification or further differentiation of individual DRGs within the existing G-DRG-system. Even in DRGs for which a differentiation would be possible and economically appropriate it is often not permitted. A further rise of the systematic deficit of German University Hospitals (currently 300 Mio. Euro annually) can only be prevented by introducing either a case-based DRG-System-Surcharge for University Hospitals or by separation of a University Hospital U-DRG-System from the general G-DRG-System.

The Clinical and Socio-Economic Relevance of Increased IPMN Detection Rates and Management Choices.

BACKGROUND: Increased usage of computed tomography and magnetic resonance imaging has led to a large increase in identified pancreatic cysts of up to 25% in population-based studies. The clinical and economic relevance of identifying so many cystic lesions has not been established. Compared to other organs such as liver or kidney, dysontogenetic pancreatic cysts are rare. Pancreatic cysts comprise a variety of benign, premalignant or malignant lesions; however, precise diagnosis before resection has an accuracy of only 80%. The focus of recent research was the malignant potential of intraductal papillary mucinous neoplasms (IPMN) with the aim of establishing clinical pathways addressing risk of malignancy, age and comorbidity, treatment-related morbidity and mortality as well as cost-effectiveness of treatment and surveillance. The focus of this review is to analyze the clinical and socio-economic relevance as well as the cost-benefit relation for IPMNs. METHODS: For analysis, the following MESH terms were used to identify original articles, reviews, and guidelines in PubMed: ('intraductal papillary mucinous neoplasm' OR 'pancreatic cysts') and (incidence OR relevance OR socio-economic OR economic OR cost-effectiveness OR cost-benefit). The retrieved publications were reviewed with a focus on clinical and socio-economic relevance in relation to the increasing incidence of IPMN. RESULTS: Addressing the increasing prevalence of pancreatic cystic lesions, recent consensus guidelines suggested criteria for risk stratification according to 'worrisome features' and 'high-risk stigmata'. Recent prospective cohort studies evaluated whether these can be applied in clinical practice. Evaluation of three different clinical scenarios with regard to costs and quality-adjusted life years suggested a better effectiveness of surveillance after initial risk stratification by endoscopic ultrasound-guided fine-needle aspiration with cyst fluid analysis compared with immediate resection or follow-up without further intervention. Of interest, the 'immediate surgery' strategy was lowest for cost-effectiveness. CONCLUSIONS: The increasing incidence of identified pancreatic cysts requires an improved strategy for non-invasive risk stratification based on advanced imaging strategies. In light of a malignancy risk of 2% for branch-duct IPMN, the socio-economic necessity of a balance between surveillance and resection has to be agreed on.

Development, external validation, and comparative assessment of a new diagnostic score for hepatic steatosis.

OBJECTIVES: We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI) in determining individual risk of hepatic steatosis. We also developed a new risk scoring system and validated all three indices using external data. METHODS: We used data from the Study of Health in Pomerania (SHIP; n=4,222), conducted in North-eastern Germany, to validate the existing scoring systems and to develop our own index. Data from the South German Echinococcus Multilocularis and Internal Diseases in Leutkirch (EMIL) study (n=2,177) were used as an external validation data set. Diagnostic performance was evaluated in terms of discrimination (area under the receiver operating characteristic curve (AUC)) and calibration plots. We applied boosting for generalized linear models to select relevant diagnostic separators. RESULTS: The FLI accurately discriminated patients with fatty liver disease from those without (AUC=0.817) but had poor calibration, in that predicted risks differed considerably from observed risks, based on SHIP data. The FLI performed well in discrimination and calibration in the analysis of EMIL data (AUC=0.890). The HSI performed worse than the FLI in analysis of both data sets (SHIP: AUC=0.782 and EMIL: AUC=0.841), showing an extremely skewed calibration. Our newly developed risk score had a good performance in the development data set (SHIP: AUC=0.860) and also good discrimination ability in the validation data (EMIL: AUC=0.876), but it had low calibration based on the validation data set. CONCLUSIONS: We compared the ability of the FLI, HSI, and our own scoring system to determine the risk of hepatic steatosis using two population-based data sets (one for the development of our own system and one for validation). In the development and independent replication data set, all three indices discriminated well between patients with and without hepatic steatosis, but the predicted risks did not match well with the observed risks, when applied to external data. Scoring systems for fatty liver disease could depend on methodological standardization of ultrasound diagnosis and laboratory measurements.

Secretin-stimulated MRCP in volunteers: assessment of safety, duct visualization, and pancreatic exocrine function.

OBJECTIVE: The objective of our study was to investigate secretin-stimulated MRCP in terms of the safety of secretin, improvement of duct visualization, and assessment of pancreatic exocrine function. MATERIALS AND METHODS: Eight hundred sixteen volunteers (370 women and 446 men; mean age, 49.7 ± 13.1 [SD] years) underwent 3D MRCP before and after secretin stimulation (1 U/kg of body weight) at 1.5 T. For the first 2 hours after secretin injection, subjects were evaluated for adverse reactions. Improvement of duct visualization after secretin stimulation was subjectively evaluated by two readers and was quantified by duct diameter measurements. Pancreatic exocrine function was evaluated subjectively by two readers according to the duodenal filling and was quantified using calibrated volumetric measurements of total excreted volume and pancreatic flow output. RESULTS: Two subjects (0.2%) showed flushing (minor adverse reaction). Duct visualization after secretin injection was improved for reader 1 in 468 (57.4%) and for reader 2 in 478 (58.6%) subjects, was unchanged for reader 1 in 324 (39.7%) and for reader 2 in 315 (38.6%) subjects, and was worse for reader 1 in 24 (2.9%) and reader 2 in 23 (2.8%) subjects (interrater agreement, κ = 0.925). Main pancreatic duct diameters increased significantly after secretin stimulation: pancreatic head, 10.5% (mean); body, 12.5%; and tail, 7.7%. Pancreatic exocrine function evaluated according to assessment of duodenal filling was as follows: grade 0 (restricted function) in 0.7% of subjects by both readers, grade 1 (reduced function) in 4.8% of subjects by reader 1 and 4.5% of subjects by reader 2, grade 2 (low-grade reduced function) in 31.1% of subjects by reader 1 and 26.5% of subjects by reader 2, and grade 3 (physiologic function) in 63.4% of subjects by reader 1 and 68.3% of subjects by reader 2 (interrater agreement, κ = 0.838). The mean total excreted volume was 111.8 ± 49.8 (SD) mL, and the mean pancreatic flow output was 9.6 ± 4.2 mL/min. CONCLUSION: Secretin-stimulated MRCP moderately improves main pancreatic duct visualization and allows noninvasive quantification of pancreatic exocrine function with a negligible risk of side effects.

Ubiquitin ligases of the N-end rule pathway: assessment of mutations in UBR1 that cause the Johanson-Blizzard syndrome.

BACKGROUND: Johanson-Blizzard syndrome (JBS; OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, facial dysmorphism with the characteristic nasal wing hypoplasia, multiple malformations, and frequent mental retardation. Our previous work has shown that JBS is caused by mutations in human UBR1, which encodes one of the E3 ubiquitin ligases of the N-end rule pathway. The N-end rule relates the regulation of the in vivo half-life of a protein to the identity of its N-terminal residue. One class of degradation signals (degrons) recognized by UBR1 are destabilizing N-terminal residues of protein substrates. METHODOLOGY/PRINCIPAL FINDINGS: Most JBS-causing alterations of UBR1 are nonsense, frameshift or splice-site mutations that abolish UBR1 activity. We report here missense mutations of human UBR1 in patients with milder variants of JBS. These single-residue changes, including a previously reported missense mutation, involve positions in the RING-H2 and UBR domains of UBR1 that are conserved among eukaryotes. Taking advantage of this conservation, we constructed alleles of the yeast Saccharomyces cerevisiae UBR1 that were counterparts of missense JBS-UBR1 alleles. Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients. CONCLUSIONS/SIGNIFICANCE: These results, made possible by modeling defects of a human ubiquitin ligase in its yeast counterpart, verified and confirmed the relevance of specific missense UBR1 alleles to JBS, and suggested that a residual activity of a missense allele is causally associated with milder variants of JBS.