Are costs derived from diagnosis-related groups suitable for use in economic evaluations? A comparison across nine European countries in the European Healthcare and Social Cost Database

The European Journal of Health Economics - Economic evaluation of health technologies requires healthcare resources, procedures and services to be valued at their opportunity cost. In practice,...     

Resumen ejecutivo del Documento de Consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y de la Asociación Española de Cirujanos (AEC) en profilaxis antibiótica en cirugía

Antibiotic prophylaxis in surgery is one of the most effective measures for preventing surgical site infection, although its use is frequently inadequate and may even increase the risk of infection, toxicities and antimicrobial resistance. As a result of advances in surgical techniques and the emergence of multidrug-resistant organisms, the current guidelines for prophylaxis need to be revised.The Sociedad Española de Enfermedades Infecciosas (Spanish Society of Infectious Diseases and Clinical Microbiology) (SEIMC) together with the Asociación Española de Cirujanos (Spanish Association of Surgeons) (AEC) have revised and updated the recommendations for antibiotic prophylaxis in surgery to adapt them to any type of surgical intervention and to current epidemiology. This document gathers together the recommendations on antimicrobial prophylaxis in the various procedures, with doses, duration, prophylaxis in special patient groups, and in epidemiological settings of multidrug resistance to facilitate standardized management and the safe, effective and rational use of antibiotics in elective surgery.     

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

The role of p53 tumor-associated protein in colon cancer detection and prevention (Review)

The role of the cytoplasmic fraction of p53 protein in the detection and prevention of colon cancer was analyzed by comparing results of the author's studies with data published in the literature. In cancer detection, although immunochemical methods are widely used for diagnostic purposes positive results are not always obtained. Using a new modification of affinity chromatography columns, we isolated the cytoplasmic, soluble form of tumor-associated antigens (TAA) from the serum of colon cancer patients. p53 protein was found to be one of the main components of such TAA. The serum level of p53 antigen was related to tumorigenicity: the correlation and regression coefficients between the serum level of p53 protein and the progress in colon cancer were 0.48 and 0.88, respectively, p<0.01. Thus HPLC-determination of the serum concentration of this protein could serve as a screening tool for cancer detection. The sensitivity and specificity of the method reached 92% and its accuracy was 88%. The method can be used to detect cancer development either as a primary disease or as a recurrent disorder. In cancer prevention, a few attempts have been made to utilize p53 protein as a tumor suppressor. IgG generated against the cytoplasmic p53 antigen from tumor-bearing rats prevents the carcinogenic effect of 1,2-dimethylhydrazine decreasing significantly the number of tumor-bearing rats in vaccinated group compared with non-vaccinated controls. Anti-p53 IgG not only had an antitumor effect but also prevents benign tumors from becoming malignant: the number of malignant tumors in vaccinated rats was half that in controls (29% and 58%, respectively). The antitumor effect of vaccination is accompanied with a significant increase in the serum-level of p53 antigen in vaccinated rats compared with non-vaccinated controls. p53 protein plays an important role in colon cancer: the unique mechanism involved in both cancer development and in cancer prevention appears to include high production of this protein.     

The role of dietary factors in prevention of chemically-induced cancers (review)

The role of dietary factors in prevention of chemically-induced cancer was reviewed on two models: i) the role of high fiber diets in prevention of colon cancer and ii) the role of high fat diets in prevention of mammary gland cancer, i) Experiments in colon cancer showed that 20% cellulose content decreased tumor incidence caused by 1,2-dimethylhydrazine (DMH) to 33% compared with 92% of tumors developed in animals fed a fiber-free diet. The tumor-preventive effect of a cellulose diet was accompanied by increased enzyme concentrations, such as ornithine decarboxylase, thymidine kinase and beta-glucuronidase. Corncob fiber (15%), treated with the fungus Pleurotus os., had a significant protective effect against DMH-induced rat colon cancer. This effect was accompanied by activation of some cellular mechanisms, i.e. apoptosis, proliferating cell nuclear antigen (PCNA) and p53 protein synthesis. A high positive correlation was found between tumor grade and p53 protein in the serum (r=0.97) or in the cell cytoplasm (r=0.77), and between tumor grade and PCNA (r=0.81). An inverse relationship was found between tumor grade and apoptosis (r=-0.63). ii) Experiments in mammary gland cancer showed that a 15% olive-oil diet reduced tumor incidence caused by 9,10-dimethyl-1,2-benzanthracene to 30%, compared with 55% in the control group. The antitumor effect of the olive oil diet was connected to its content of monounsaturated fatty acids, such as oleic and palmitic acids. The promotive tumorigenic effects of other high-fat diets (avocado, soybeans) were associated with high content of some polyunsaturated fatty acids (linoleic and alpha-linolenic). We concluded that different diets have different targets. The effect of the same diet depends on its content of anti-tumor substances.     

The tumorigenic phenotype of a mutated form of Fc gamma RIIB1, lacking the ability to generate soluble receptor and allowing a low-level of ligand binding

Non immunohematopoietic murine tumor cells ectopically expressing Fc gamma RIIB1 (B1) were recently shown to express a higher tumorigenicity phenotype than cells not expressing this receptor. Utilizing a genetic approach we studied the possible contribution of a soluble form of B1 to tumor enhancement. A mutated form of the B1, lacking the cleavage site responsible for the generation of soluble B1 was produced using gene splicing by overlap extension PCR. A deletion confirmed by sequence analysis from 172 to 178 residues was generated. Stable transfectants expressed the B1 deleted form (B1 Delta) both as specific RNA and as a membrane protein receptor allowing a low level of ligand binding. The soluble form of B1 was undetectable in tissue culture supernatants of Bib transfected cells while it was present in supernatants of wild type B1-transfectants. Stable B1 Delta transfectants were significantly more tumorigenic than negative control transfectants. Tumor incidence was almost as high as that of intact B1 and lagged in the latency period before the appearance of palpable tumors. It is suggested that the soluble B1 has a minimal contribution to tumor enhancement.     

Androgenic Activity of Antiandrogens Predicted by Fit into DNA

Computer modeling including graphics and energy calculations were employed for the first time to examine the stereochemical fit of antiandrogens into double-stranded DNA. In this study, we assessed the relative fit of antiandrogens in the cavity between base pairs known to accommodate androgens. When compared to testosterone which was given a normalized value of 100%, the antiandrogens manifested the following order of fit: RU23908 (88%) > hydroxyflutamide (71%) > cyproterone acetate (41%). A correlation was observed between the relative fit of the antiandrogens and reported agonistic properties as assessed by the ability to increase nuclear androgen receptor levels in the rat ventral prostate. These findings may be useful in the design and development of androgen antagonists without agonistic activity.     

Oleanolic acid promotes healing of acetic acid-induced chronic gastric lesions in rats.

PURPOSE: Previous work demonstrates that oleanolic acid (OA), a triterpene widely distributed in plants, shows gastroprotective effect in the ethanol, aspirin and pilorous ligature-induced gastric ulcer in rats as well as in the ethanol/hydrochloric acid-induced ulcer in mice. The aim of this work was to assess the healing effect of OA in the acetic acid-induced chronic gastric ulcer model in rats. METHODS: Chronic gastric lesions were induced in male Sprague-Dawley rats with acetic acid. OA was administered orally during 14 days at 25, 50 and 100 mg/kg per day. Ranitidine (50 mg/kg) and the vehicle were used as controls. The ulcer area (mm2) and the curative ratio (%) were determined. Histological preparations were carried out for comparative purposes. RESULTS: The effect of OA was significantly different as compared to the control reducing the lesion area (in mm2) from 39+/-7 in controls to 17.8+/-1.9 and 9.4+/-1.1 at the doses of 50 and 100 mg/kg, respectively. The curative ratio was 54.5 and 76% for the compound at 50 and 100 mg/kg, while ranitidine at 50 mg/kg reduced the lesion area to 6.9+/-0.8 with a curative ratio of 84%. Mucosal thickness increased from 342 microm in controls to 540 microm in oleanolic acid- (100 mg/kg) and 945 microm in ranitidine-treated animals. Histological examination of the stomach showed regeneration of the lesions. CONCLUSIONS: OA improves healing of chronic gastric lesions in rats. The low toxicity and widespread occurrence of OA in plants suggest a potential for the development of the triterpene or their derivatives as a new antiulcer drug.     

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.