Relevance of hospital characteristics as performance indicators for treatment of very-low-birth-weight neonates.

BACKGROUND: Current attempts at centralization of neonatal care in Germany focus on a minimum volume of 30 very-low-birth-weight (VLBW, weighing <1250 g) neonate admissions per year. However, the evidence for a selective referral strategy based on hospital volume is unclear. METHOD: A total of 5575 neonates weighing <1250 g treated in 31 hospitals in Bavaria between 2000 and 2011 were analysed using population-based data. The relevance of different hospital characteristics (i.e. hospital volume, bed capacity and teaching status) for explaining individual in-hospital mortality as well as interhospital variation in mortality rates was analysed using multilevel logistic regression analysis. RESULTS: In a risk-adjusted model, only dichotomized hospital volume (<30 admissions) was significantly associated with higher mortality in VLBW neonates (odds ratio: 1.74; 95% confidence interval: 1.02-2.99). However, the higher mortality risk only applied to neonates with higher Clinical Risk Index for Babies (CRIB) scores. There was considerable heterogeneity in mortality rates between Bavarian hospitals. The median odds ratio for mortality between two neonates treated in a randomly chosen low-performing versus high-performing hospital was 1.62 in the null model (without explanatory variables). Hospital volume only explained 15.1% of interhospital variation in mortality rates after adjustment for case-mix. Other hospital characteristics were of minor relevance. A funnel plot of the standardized mortality ratio against the number of admissions showed that 41% of small-volume hospitals performed better than expected. CONCLUSION: A selective referral strategy based solely on hospital volume will fall short of the task of optimal allocation of neonatal care by means of centralization.

Glucagon-like peptide-1(9-36) inhibits chemokine-induced migration of human CD4-positive lymphocytes.

INTRODUCTION: Inhibitors of dipeptidyl peptidase-IV (DPP-IV), which decrease the degradation of glucose-lowering GLP-1(7-36) to the metabolically inactive GLP-1(9-36), are current new treatment options for patients with type 2 diabetes mellitus, a high-risk population for cardiovascular disease. However, the effects of the metabolite GLP-1(9-36) on atherosclerosis are unknown. Thus, the present study examined the effect of GLP-1(9-36) on chemokine-induced CD4-positive lymphocyte migration as one of the early and critical steps in atherogenesis. METHODS AND RESULTS: Stimulation of isolated human CD4-positive lymphocytes with SDF-1 led to a 3.4 fold (p<0.001; n = 7) increase in cell migration. Pretreatment of cells with GLP-1(9-36) reduced this effect in a concentration-dependent manner by 41% to a 2.0 fold induction at 10 nmol/L GLP-1(9-36) (p<0.001 compared to SDF-1-treated cells, n = 7). Similar effects were obtained when RANTES was used as a chemokine to induce cell migration. The action of GLP-1(9-36) on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity. Downstream in the PI-3 kinase signaling pathway, GLP-1(9-36) inhibited SDF-1-induced phosphorylation of MLC and cofilin and decreased f-actin formation as well as ICAM3 translocation as shown by Western blotting, flow cytometry and immunohistochemistry, respectively. However, the effect of GLP-1(9-36) on PI-3 kinase signaling was not associated with increased intracellular levels of cAMP. Furthermore, experiments with siRNA demonstrated that the inhibitory effect of GLP-1(9-36) on SDF-1-induced ICAM3-translocation was preserved in human CD4-positive lymphocytes lacking the GLP-1 receptor, suggesting signaling independent of the known GLP-1 receptor. CONCLUSION: Thus, GLP-1(9-36) inhibits chemokine-induced CD4-positive lymphocyte migration by inhibition of the PI3-kinase pathway independent of cAMP and GLP-1 receptor signaling. Further studies are needed to assess whether such effects may be clinically relevant for patients with type 2 diabetes treated with DPP-IV inhibitors.