Clinical and economic impact of implementing a comprehensive diabetes management program in managed care

Diabetes mellitus places a significant burden on the U.S. healthcare system. Because of the potential to reduce diabetic complications and costs through intensive management, diabetes has become a primary target for disease management programs. We performed a retrospective analysis of short-term baseline and follow-up clinical, economic, and member and provider satisfaction data from approximately 7,000 people with diabetes being treated through seven managed care plans using Diabetes Treatment Centers of America's Diabetes NetCare, (Nashville, TN), a comprehensive diabetes management program. Our analysis indicates that Diabetes NetCare achieved gross economic adjusted savings of $50 per diabetic member per month (12.3%), with gross unadjusted savings of $44 (10.9%) per diabetic member per month. Hospital admissions per 1,000 diabetic member years decreased by 18%, and bed days fell by 21%. Patients with diabetes were more likely to get HbAlc tests, foot exams, eye exams, and cholesterol screenings while enrolled in the program. These data suggest that implementation of a comprehensive healthcare management program for people with diabetes can lead to substantial improvements in costs and clinical outcomes in the short-term. It is expected that improvements will increase over time, with continuing improvements in health status and a reduction in the number of future diabetic complications.     

The prospects for using the genetically engineered surface antigen of the hepatitis B virus (HBsAg) expressed by recombinant poxvirus strains as the basis for vaccines against hepatitis B

The use of a recombinant poxvirus (RPV) strain, expressing HBsAg in the process of reproduction in different bioreactor systems under stationary and bioreactor conditions of cultivation, made it possible to obtain highly purified HBsAg. The identity and purity of HBsAg was confirmed by the analysis of its amino acid composition, SDS electrophoresis in polyacrylamide gel, electron microscopy and high-performance liquid chromatography. Good prospects of the use of RPV-expressed gene engineering HBsAg as the basis vaccines against hepatitis B was demonstrated in 10 experimental batches of vaccine. All batches of the preparation had pronounced immunogenicity and were safe and nontoxic in animal experiments. The ID50 of experimental batches did not exceed 211 ng/ml, which, according to the data of comparative experiments, was lower than, or equal to, corresponding values of analogous foreign commercial preparations, based on plasma or yeast HBsAg.     

Preferred strategies for secondary infrainguinal bypass: lessons learned from 300 consecutive reoperations

PURPOSE: To determine the optimal surgical strategies in reoperative infrainguinal bypass, we reviewed our results in 300 consecutive secondary bypasses in 251 patients operated on between Jan. 1, 1975, and Nov. 1, 1993. METHODS: There were 168 men (67%) and 83 women (33%), with a mean age of 64.8 years and a typical distribution of risk factors including smoking (76.4%), diabetes (33.7%), and coronary artery disease (47.1%). The indications for surgery were limb-threatening ischemia in 83.5% and severe claudication in 16.5% of patients. The majority of conduits (n = 213) were autogenous vein and were composed of a single segment of greater saphenous vein in 121 bypasses (57%) and various alternative veins including composite, arm, and lesser saphenous vein in 92 bypasses (43%). Prosthetic conduits included 69 polytetrafluoroethylene, 16 umbilical vein, and two Dacron grafts. RESULTS: There was one perioperative death (0.3%) and a 25% total morbidity rate including a 1.7% myocardial infarction rate. There was a 28.6% early (< 30 days) graft failure and 10.7% early amputation rate for prosthetic bypass grafts compared with 13.6% early graft failure and 5.6% early amputation rates for vein grafts. Autogenous vein bypasses had higher 5-year secondary patency rates than had prosthetic grafts (51.5% +/- 4.6% vs 27.4% +/- 6.1%, p < 0.001). Results with autogenous vein bypass improved significantly from the 1975 to 1984 to the 1985 to 1993 interval with 5-year secondary patency rates increasing from 38.3% +/- 6.9% to 59.1% +/- 5.8% (p = 0.017) and 5-year limb-salvage rates increasing from 40.4% +/- 7.6% to 72.4% +/- 6.6% (p < 0.001). Vein grafts to the popliteal and tibial outflow levels had equivalent long-term results. Vein grafts completed for claudication demonstrated results superior to those for limb salvage, with a 5-year secondary patency rate of 75.8% +/- 8.1% versus 52.3% +/- 7.9% (p = 0.048). Secondary autogenous vein bypass grafting performed after early primary graft failure (< 3 months) did particularly poorly, with only a 27.2% +/- 7.7% 4-year secondary patency rate. Greater saphenous veins tended to perform better than alternative vein bypasses, with a 5-year secondary patency rate of 68.5% +/- 6.0% compared with 48.3% +/- 10.5% (p = 0.09) and a 5-year limb-salvage rate of 77.8% +/- 7.4% versus 54.2% +/- 11.8% (p = 0.046). CONCLUSIONS: When patients suffer a recurrence of limb-threatening ischemia at the time of infrainguinal graft failure, aggressive attempts at secondary revascularization with autogenous vein are warranted based on the low surgical morbidity and mortality rates and the improved patency and limb salvage rates that are currently attainable.     

CBF beta-SMMHC, expressed in M4Eo AML, reduced CBF DNA-binding and inhibited the G1 to S cell cycle transition at the restriction point in myeloid and lymphoid cells

CBF beta-SMMHC is expressed from the inv(16) chromosome in M4Eo AML. Mice lacking CBF subunits or expressing the CBF beta-SMMHC or AML1-ETO oncoproteins failed to develop definitive hematopoiesis. To investigate these effects on hematopoiesis, we expressed CBF beta-SMMHC from the metallothionein promoter, in both 32D cl3 myeloid cells and Ba/F3 B-lymphoid cells. Addition of zinc increased CBF beta-SMMHC levels more than tenfold, with higher levels evident in Ba/F3 lines. Levels obtained in 32D cl3 cells were similar to those of endogenous CBF beta. Indirect immunofluorescence revealed zinc-inducible speckled, nuclear staining in Ba/F3 cells and diffuse nuclear staining in 32D cl3 cells. CBF beta-SMMHC reduced endogenous CBF DNA-binding fivefold in both cell types, increased cell generation time 1.9-fold, on average, in 32D cl3 cells and 1.5-fold in Ba/ F3 cells and decreased tritiated thymidine incorporation into DNA correspondingly. CBF beta-SMMHC increased the proportion of cells in G1 1.7-fold, on average, in 32D cl3 and Ba/F3 cells, and decreased the proportion of cells in S phase by a similar degree. CBF beta-SMMHC induced a marked increase in hypophosphorylated Rb, but did not alter IL-3 Receptor alpha or beta subunit levels. Neither apoptosis nor 32D differentiation was induced by zinc in IL-3 in these lines. Induction of CBF beta-SMMHC in 32D cl3 cells did not inhibit their differentiation to neutrophils or their expression of myeloperoxidase mRNA in G-CSF, and did not produce an eosinophilic phenotype. Additional, proliferative genetic changes in M4eo AMLs might potentiate inhibition of differentiation by CBF beta-SMMHC by allowing its increased expression.     

Tissue factor pathway inhibitor in endothelial cells colocalizes with glycolipid microdomains/caveolae. Regulatory mechanism(s) of the anticoagulant properties of the endothelium

Tissue factor pathway inhibitor (TFPI), the main downregulator of the procoagulant activity of tissue factor.factor VIIa complex, locates in human endothelial cells (EC) in culture as well-defined clusters uniformly distributed both on the cell surface and intracellularly. We here demonstrate by immunofluorescence that TFPI colocalizes in EC with caveolin, urokinase-type plasminogen activator receptor, and glycosphingolipids. The localization of TFPI in caveolae in resting endothelium is proved by double immunogold electron microscopy for TFPI and caveolin. After ultracentrifugation of rat lung or EC homogenates through density gradients of Nycodenz, TFPI was highly enriched at densities of 1.05 to 1.08 g/mL, together with caveolin and alkaline phosphatase. By ELISA, more than half of the cellular TFPI was detected in Triton X-100-insoluble extracts of EC. TFPI incorporates [1-3H]ethanolamine and is cleaved from the cell surface by phosphatidylinositol-phospholipase C, indicating a specific glycosylphosphatidylinositol-anchorage mechanism for TFPI in the plasma membrane. Clustering of TFPI and its localization in caveolae are dependent on the presence of cholesterol in the membrane. Agonist-induced stimulation of EC caused marked changes of distribution for both TFPI and caveolin at subcellular level, with subsequent increase of the cell surface-associated inhibitory activity toward tissue factor.factor VIIa. Our findings suggest that, beside their function in transcytosis, potocytosis, cell surface proteolysis, and regulation of signal transduction, caveolae also play a direct role in the regulation of EC anticoagulant properties.