Clinical implications and economic impact of accuracy differences among commercially available blood glucose monitoring systems.

BACKGROUND: Despite accuracy standards, there are performance differences among commercially available blood glucose monitoring (BGM) systems. The objective of this analysis was to assess the potential clinical and economic impact of accuracy differences of various BGM systems using a modeling approach. METHODS: We simulated additional risk of hypoglycemia due to blood glucose (BG) measurement errors of five different BGM systems based on results of a real-world accuracy study, while retaining other sources of glycemic variability. Using data from published literature, we estimated an annual additional number of required medical interventions as a result of hypoglycemia. We based our calculations on patients with type 1 diabetes mellitus (T1DM) and T2DM requiring multiple daily injections (MDIs) of insulin in a U.S. health care system. We estimated additional costs attributable to treatment of severe hypoglycemic episodes resulting from BG measurement errors. RESULTS: Results from our model predict an annual difference of approximately 296,000 severe hypoglycemic episodes from BG measurement errors for T1DM (105,000 for T2DM MDI) patients for the estimated U.S. population of 958,800 T1DM and 1,353,600 T2DM MDI patients, using the least accurate BGM system versus patients using the most accurate system in a U.S. health care system. This resulted in additional direct costs of approximately $339 million for T1DM and approximately $121 million for T2DM MDI patients per year. CONCLUSION: Our analysis shows that error patterns over the operating range of BGM meter may lead to relevant clinical and economic outcome differences that may not be reflected in a common accuracy metric or standard. Further research is necessary to validate the findings of this model-based approach.

Actionable self-monitoring of blood glucose: redefining the role for patients using multiple daily injection therapy.

Self-monitoring of blood glucose (SMBG) values is an accepted requirement for patients with diabetes using multiple daily injections of insulin. Nevertheless, for many patients, the full value of SMBG has yet to be realized due to a number of factors that contribute to patients not taking appropriate action based on the achieved result. The reasons for this are complex but are related to the burden imposed by performing the tests, the need for complex numerical calculations, and the demand for undertaking this activity multiple times each day. In the near future, SMBG devices are likely to include technological innovations that are aimed at overcoming these barriers, offering "actionable" SMBG for patients using insulin. These innovations should include technologies that will allow customization and individualization based upon specific therapy regimens.

Cost-effectiveness of linezolid versus vancomycin for hospitalised patients with complicated skin and soft-tissue infections in Germany.

This study used a decision analytic model approach to evaluate the cost-effectiveness of linezolid versus vancomycin in the empirical treatment of complicated skin and soft-tissue infection (cSSTI) due to suspected methicillin-resistant Staphylococcus aureus (MRSA) from the German hospital and health care system perspective. Clinical probabilities were obtained from trial data, resource utilisation and MRSA prevalence rates were obtained through German physician interviews, and costs from published sources were applied to resource units. Outcomes included total cost/patient and cure. The estimated first-line cure rate for linezolid-treated patients was 90.1% versus 85.5% for vancomycin; total cure rates after two lines of treatment were 98.4% and 98.1%, respectively. Average total cost/episode was 8,232 euro for linezolid versus 9,206 euro for vancomycin. The model outcomes were sensitive to changes in length of stay (LOS), isolation days, rate of confirmed MRSA and price of linezolid. Linezolid was expected to result in a shorter intravenous treatment duration and shorter LOS that offset its higher acquisition cost versus vancomycin in cSSTI in Germany.

The cost of resistance: incremental cost of methicillin-resistant Staphylococcus aureus (MRSA) in German hospitals.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in many healthcare systems. In Germany, few data are available on its economic consequences and, so far, no study has been performed using a large sample of real-life data from several hospitals. We present a retrospective matched-pairs analysis of mortality, length of stay, and cost of MRSA patients based mainly on routine administrative data from 11 German hospitals. Our results show that MRSA patients stay in hospital 11 days longer, exhibit 7% higher mortality, are 7% more likely to undergo mechanical ventilation, and cause significantly higher total costs ( 8,198).

The economic costs of overactive bladder in Germany.

OBJECTIVE: To estimate the annual direct costs of overactive bladder (OAB) in Germany from a societal perspective. METHODS: Direct costs were calculated based on prevalence figures and medical resource utilisation due to hospitalisation, office-based physician visits, visits to other health care professionals, medication, medical aids and devices, and nursing care. RESULTS: A total of 6.48 million adults>or=40 yr of age in Germany are affected by OAB, and 2.18 million of these individuals experience incontinence. The annual incidence of comorbidities attributable to OAB is 310,000 for skin infections, 40,000 for falls, 12,000 for fractures, and 26,000 for depression (based on 2004 census data). Direct OAB-related costs per year are euro3.98 billion, with euro1.76 billion covered by statutory health insurance, euro1.80 billion by nursing care insurance, and euro0.41 billion by the patients. Nursing care accounts for euro1.80 billion of total costs (45%), devices account for euro0.68 billion (17%), physician visits account for euro0.65 billion (16%), complications account for euro0.75 billion (19%), and medication accounts for euro0.08 billion (2%). CONCLUSION: OAB imposes a substantial economic burden on German health and nursing care, insurance, and on patients with OAB. Direct annual costs are comparable to those of other chronic diseases such as dementia or diabetes mellitus.

Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression.

Oncostatin M has been characterized as a potent growth inhibitor for various tumor cells. Oncostatin M-treated glioblastoma cells cease proliferation and instigate astrocytal differentiation. The oncostatin M-induced cell cycle arrest in G(1) phase is characterized by increased level of the cyclin-dependent kinase (CDK) inhibitory proteins p21(Cip1/Waf1/Sdi1) and p27(Kip1). Induction of p21 protein corresponds to increased mRNA level, whereas p27 accumulates due to increased stability of the protein. Interestingly, stabilization of p27(Kip1) occurs even in S phase, showing that p27 stabilization is a direct consequence of oncostatin M signaling and not a result of the cell cycle arrest. Degradation of p27 in late G(1) and S phase is initiated by the ubiquitin ligase complex SCF-Skp2/Cks1. Oncostatin M inhibits expression of two components of this E3 ligase complex (Skp2 and Cks1). Although combined overexpression of Skp2 and Cks1 rescues p27 degradation in S phase, it can not override p27 accumulation in G(1) phase and cell cycle arrest by oncostatin M. In addition to increasing Cdk inhibitor level, oncostatin M also impairs cyclin A expression. Cyclin A mRNA and protein level decline shortly after oncostatin M addition. The accumulation of two CDK inhibitor proteins and the repression of cyclin A expression may explain the broad and potent antiproliferative effect of the cytokine.

Economic evaluation of voriconazole versus conventional amphotericin B in the treatment of invasive aspergillosis in Germany.

OBJECTIVE: To assess the costs and cost-effectiveness of voriconazole in comparison to conventional amphotericin B (CAB) for the treatment of invasive aspergillosis in Germany. METHODS: The cost-effectiveness of voriconazole in comparison to CAB was evaluated with a lifetime Markov model, focusing on the long-term survival of patients treated for invasive aspergillosis. Long-term survival was extrapolated from survival after 12 weeks of treatment, obtained from a randomized aspergillosis study. Information on medical resource consumption and treatment pathways were obtained from this study and an expert committee. With probabilistic analysis the cost-effectiveness of voriconazole compared with amphotericin B was analyzed and expressed in incremental costs per life-weeks gained. The evaluation was performed from a limited societal perspective (both inpatient and outpatient costs) and hospital perspective (only inpatient costs). RESULTS: Average survival of patients treated with voriconazole was 174.4 life-weeks (95% confidence interval [CI] 159.4-191.3), compared with 119.4 life-weeks (95% CI 106.4-132.3) for amphotericin B. With voriconazole, the mean total costs per patient were 30,026 euros (95% CI 23 euros ,118-37,947) compared with 26,669 euros for amphotericin B (95% CI 21,259-34,263 euros ) from the limited societal perspective. The corresponding incremental cost-effectiveness ratio was 62 euros per life-week gained (i.e., 3224 euros per life-year gained). Hospital costs were approximately 90% of the mean total costs. CONCLUSIONS: In the treatment of invasive aspergillosis, voriconazole is cost-effective in comparison to amphotericin B. Hospital costs are comparable for both treatments and are expected to be reimbursed based on the German diagnosis-related groups (DRG) system 2005.

Aptamers--basic research, drug development, and clinical applications.

Since its discovery in the early 1990s, aptamer technology has progressed tremendously. Automated selection procedures now allow rapid identification of DNA and RNA sequences that can target a broad range of extra- and intracellular proteins with nanomolar affinities and high specificities. The unique binding properties of nucleic acids, which are amenable to various modifications, make aptamers perfectly suitable for different areas of biotechnology. Moreover, the approval of an aptamer for vascular endothelial growth factor by the US Food and Drug Administration highlights the potential of aptamers for therapeutic applications. This review summarizes recent developments and demonstrates that aptamers are valuable tools for diagnostics, purification processes, target validation, drug discovery, and even therapeutic approaches.

Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

BACKGROUND: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating. METHODS AND RESULTS: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining. CONCLUSIONS: Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.

CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis.

We show that p27 localization is cell cycle regulated and we suggest that active CRM1/RanGTP-mediated nuclear export of p27 may be linked to cytoplasmic p27 proteolysis in early G1. p27 is nuclear in G0 and early G1 and appears transiently in the cytoplasm at the G1/S transition. Association of p27 with the exportin CRM1 was minimal in G0 and increased markedly during G1-to-S phase progression. Proteasome inhibition in mid-G1 did not impair nuclear import of p27, but led to accumulation of p27 in the cytoplasm, suggesting that export precedes degradation for at least part of the cellular p27 pool. p27-CRM1 binding and nuclear export were inhibited by S10A mutation but not by T187A mutation. A putative nuclear export sequence in p27 is identified whose mutation reduced p27-CRM1 interaction, nuclear export, and p27 degradation. Leptomycin B (LMB) did not inhibit p27-CRM1 binding, nor did it prevent p27 export in vitro or in heterokaryon assays. Prebinding of CRM1 to the HIV-1 Rev nuclear export sequence did not inhibit p27-CRM1 interaction, suggesting that p27 binds CRM1 at a non-LMB-sensitive motif. LMB increased total cellular p27 and may do so indirectly, through effects on other p27 regulatory proteins. These data suggest a model in which p27 undergoes active, CRM1-dependent nuclear export and cytoplasmic degradation in early G1. This would permit the incremental activation of cyclin E-Cdk2 leading to cyclin E-Cdk2-mediated T187 phosphorylation and p27 proteolysis in late G1 and S phase.