Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET).

BACKGROUND: The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. METHODS: TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48-72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >-10%. Safety was assessed through adverse event and laboratory data collection. RESULTS: In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: -1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. CONCLUSIONS: TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. CLINICAL TRIALS REGISTRATION: NCT03137173.

Sol-Gel Multilayered Niobium (Vanadium)-Doped TiO2 for CO Sensing and Photocatalytic Degradation of Methylene Blue.

Multilayered TiO2 films doped either with Niobium or Vanadium (1.2 at. %) were deposited by the sol-gel dip coating method on c-Si and glass substrates. The films on glass substrates were tested for CO sensing and photocatalytic degradation of methylene blue. X-ray diffraction data analysis showed that all the TiO2:Nb(V) films were nanocrystalline in the anatase phase, with a uniform and compact microstructure and a homogeneous superficial structure of small grains with diameters in the range of 13-19 nm. For the electrical characterization, the TiO2:Nb(V) films were incorporated in Metal-Insulator-Semiconductor (MIS) structures. The specific resistivity is of the order of 104 Ωcm and its value decreases with increasing the electrical field, which testifies to the injection of electrons into these layers. From the analysis of the current-voltage curves taken at different temperature- and frequency-dependent capacitance-voltage and conductance-voltage characteristics, the density and parameters of deep levels in these TiO2 films are evaluated and the electron charge transport mechanism is established. It was shown that the current in these TiO2:Nb(V)-Si MIS structures is mainly carried out by inter-trap tunneling via deep levels energetically distributed in the TiO2 bandgap. Testing these sol-gel TiO2:Nb(V) layers for gas sensing and photocatalytic capabilities proved that they could serve such purposes. In particular, the results of the V-doped sol-gel TiO2 film confirm its CO detection capability, which is rarely reported in the literature. For the photodegradation of methylene blue, the Nb-doped TiO2 samples were superior, with nearly double the photocatalytic efficiency of undoped TiO2.

Investigation of the Effects of Rapid Thermal Annealing on the Electron Transport Mechanism in Nitrogen-Doped ZnO Thin Films Grown by RF Magnetron Sputtering.

Nitrogen-doped ZnO (ZnO:N) thin films, deposited on Si(100) substrates by RF magnetron sputtering in a gas mixture of argon, oxygen, and nitrogen at different ratios followed by Rapid Thermal Annealing (RTA) at 400 °C and 550 °C, were studied in the present work. Raman and photoluminescence spectroscopic analyses showed that introduction of N into the ZnO matrix generated defects related to oxygen and zinc vacancies and interstitials. These defects were deep levels which contributed to the electron transport properties of the ZnO:N films, studied by analyzing the current-voltage characteristics of metal-insulator-semiconductor structures with ZnO:N films, measured at 298 and 77 K. At the appliedtechnological conditions of deposition and subsequent RTA at 400 °C n-type ZnO:N films were formed, while RTA at 550 °C transformed the n-ZnO:N films to p-ZnO:N ones. The charge transport in both types of ZnO:N films was carried out via deep levels in the ZnO energy gap. The density of the deep levels was in the order of 1019 cm-3. In the temperature range of 77-298 K, the electron transport mechanism in the ZnO:N films was predominantly intertrap tunneling, but thermally activated hopping also took place.

Bone lesions in malignant diseases--I. Current concepts of major pathogenetic mechanisms and forms.

Bones are among the major parts of the body that are targeted in neoplastic diseases. Bone lesions increasing in number and size and diffuse osteoporosis are found in 30-80% of cancer patients. All literature data about the pathogenetic factors of osteolytic and osteosclerotic bone lesions are classified into four groups: 1. Directly connected with the neoplastic tumour mass. 2. Humoral interaction between the tumour cells and bone cells. 3. Systemic effects and complications of the neoplastic process. 4. Extracancerous factors. We discuss here the basic pathogenetic forms of bone lesions in neoplasias: 1. Local osteolysis in the area of neoplastic infiltration. 2. Humorally activated demineralisation with hypercalcemia. 3. Light chain osteomalacia. 4. Hypophosphatemic osteomalacia. We consider the major current biochemical markers of bone remodelling and their use in diagnosing and monitoring bone disease in neoplastic conditions.

Bone lesions in malignant diseases--II. Therapeutic management.

A pathogenetically based therapeutic strategy and modality for malignant bone diseases has been created only in the last two decades. The most frequent pathogenetic defect, osteoblast/osteoclast uncoupling in the osteolytic foci and the diffuse humoral osteoporosis afford little in terms of choice of treatment which makes the inhibitors of osteoclastic activity the major medicamentous agents for their management. We discuss the mechanisms of action, pharmacokinetics, preparations and regimens of administration of biphosphonates, calcitonine and galium nitrate. Results of large double blind, placebo-controlled studies of clondronate and pamidronate in oncohematologic diseases are summarised: statistically significantly lower frequency of the osteolytic foci, pathological fractures, hypercalcemic episodes, low levels of C-L bonds, increase of bone mineral density, management of pain, and better quality of life.

Amaryl (glimepiride) in patients with type 2 diabetes mellitus.

The purpose of the present study was to investigate the effect of the first third-generation sulphonylurea drug glimepiride (Amaryl, Aventis) in the treatment of patients with type 2 diabetes mellitus in an open 6-month clinical trial. The study included 19 patients with type 2 diabetes mellitus (7 men and 12 women, aged 53.6 +/- 2.43 years, mean duration of diabetes 7.79 +/- 1.45 years). The body mass index (BMI) of the patients was x = 30.157 +/- 1.63 which is at the borderline between overweight and obesity. The patients started at a baseline dosage of 1 mg which was then it was gradually adjusted according to the blood sugar level. The dosage of the drug varied between 1 and 6 mg (mean daily dosage 2.03 mg). The metabolic control parameters that were calculated included fasting and 2-hour postprandial blood sugar concentration, total cholesterol, serum triglycerides, HbA1c, and microproteinuria. They were measured at baseline, at 3 and 6 months. The results showed that the fasting blood glucose decreased significantly (P<0.05 at 3 months and P<0.001 at 6 months). Statistically significant lower postprandial glycemia was also observed in the patients (the decrease was not significant at 3 months but highly significant at 6 months, P<0.01). The overall evaluation was based on the values of HbA1c--they were statistically significantly lower at 6 months (P<0.01) which suggests the steady improving tendency of the metabolic control in type 2 diabetes patients treated with Amaryl (glimepiride). The improvement of the metabolic control was also manifested by the lower serum triglycerides levels (P<0.05) and the BMI remaining nearly without change. It is concluded that Amaryl (glimepiride) is an efficacious oral sulphonylurea preparation which can be used as an appropriate substitute of the other beta cell stimulators. Glimepiride once daily provides a good compliance of patients which reduces to minimum the skipped doses. It is associated with a reduced risk of hypoglycemia and causes no weight gain.

Effects of Aronia melanocarpa juice as part of the dietary regimen in patients with diabetes mellitus.

The low calorie juice Aronia melanocarpa (sugar free, with artificial sweeteners) could be a valuable adjunct to the complex therapy of patients with diabetes mellitus. In this study no increased blood glucose levels were established 60 min. following ingestion of 200 ml Aronia juice. On the contrary, lower fasting blood glucose concentrations were measured in 16 patients with insulin dependent diabetes and in 25 patients with non-insulin dependent diabetes (25 women and 16 men, 3 to 62 years of age, median age 38.8 +/- 4.7) with duration of the disease from 1 month to 13 years. Serial blood glucose measurements showed: 14.23 +/- 1.32 mmol/l at baseline and 11.4 +/- 0.89 mmol/l blood glucose level after 60 min., the difference being statistically significant (p<0.05). The ingestion of 200 ml Aronia juice combined with a standard breakfast produced similar results (the basal concentration of glucose was 13.43 +/- 1.12 mmol/l; it decreased to 11.94 +/- 1.02 mmol/l at 60 min., the difference did not reach statistical significance. The daily intake of 200 ml Aronia juice over a period of 3 months was effective in lowering fasting blood glucose levels from 13.28 +/- 4.55 mmol/l to 9.10 +/- 3.05 mmol/l (p<0.001) in 21 patients with non-insulin dependent diabetes--13 women and 8 men aged from 42 to 62 (median age 53.6 +/- 3.65) with disease duration from 6 to 17 years. Aronia had a beneficial effect on HbA1c, total cholesterol and lipid levels. They dropped from 9.39 +/- 2.16% to 7.49 +/- 1.33% (p<0.001), from 6.45 +/- 1.59 mmol/l to 5.05 +/- 0.96 mmol/l (p<0.001) and from 2.92 +/- 2.15 mmol/l to 1.7 +/- 1.07 mmol/l (p<0.001), respectively. Results were compared with those obtained in 23 patients with non-insulin dependent diabetes (15 women and 8 men aged from 48 to 67 years, median age 54.9 +/- 3.34) with disease duration from 6 to 17 years. The above mentioned parameters remained unchanged in these patients. Accumulated data illustrated the hypoglycemic potential of Aronia juice. The precise mechanism of its action is unknown but its beneficial effects and good taste make it a valuable adjunct to the dietary treatment of patients with diabetes mellitus.