Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids

Molecular docking studies were performed on 18 17-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17-carboxamide steroids with potentially better biological profile than dexamethasone

Cost Analysis of Health Examination Screening Program for Ischemic Heart Disease in Active-Duty Military Personnel in the Middle-Income Country

Cardiovascular diseases, including ischemic heart disease, are the most common causes of morbidity and death in the world, including Serbia, as a middle-income European country. The aim of the study was to determine the costs of preventive examinations for ischemic heart disease in active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia population. This is a retrospective cost-preventive study which included 738 male active-duty military personnel, aged from 23 to 58. The costs of primary prevention of ischemic heart disease in this population were investigated. Out of 738 subjects examined, arterial hypertension was detected in 101 subjects (in 74 of them, arterial hypertension was registered for the first time, while 27 subjects were already subjected to pharmacotherapy for arterial hypertension). Average costs of all services during the periodic-health-examination screening program were euro76.96 per subject. However, average costs of all services during the periodic-health-examination screening program for patients with newfound arterial hypertension and poorly regulated arterial hypertension were euro767.54 per patient and euro2,103.63 per patient, respectively. Since periodic-health-examination screening program in military personnel enabled not only discovery of patient with newfound arterial hypertension but also regular monitoring of those who are already on antihypertensive therapy, significant savings of euro690.58 per patient and euro2,026.67 per patient can be achieved, respectively. As financial resources for providing health care in Serbia, as a middle-income country, are limited, further efforts should be put on screening programs for ischemic heart disease due to possible significant savings

End-of-life costs of medical care for advanced stage cancer patients

BACKGROUND/AIM: Cancer, one of the leading causes of mortality in the world, imposes a substantial economic burden on each society, including Serbia. The aim of this study was to evaluate the major cancer cost drivers in Serbia. METHODS: A retrospective, in-depth, bottom-up analysis of two combined databases was performed in order to quantify relevant costs. End-of-life data were obtained from patients with cancer, who deceased within the first year of the established diagnose, including basic demographics, diagnosis, tumour histology, medical resource use and related costs, time and cause of death. All costs were allocated to one of the three categories of cancer health care services: primary care (included home care), hospital outpatient and hospital inpatient care. RESULTS: Exactly 114 patients were analyzed, out of whom a high percent (48.25%) had distant metastases at the moment of establishing the diagnosis. Malignant neoplasms of respiratory and intrathoracic organs were leading causes of morbidity. The average costs per patient were significantly different according to the diagnosis, with the highest (13,114.10 EUR) and the lowest (4.00 EUR) ones observed in the breast cancer and melanoma, respectively. The greatest impact on total costs was observed concerning pharmaceuticals, with 42% of share (monoclonal antibodies amounted to 34% of all medicines and 14% of total costs), followed by oncology medical care (21%), radiation therapy and interventional radiology (11%), surgery (90%), imaging diagnostics (9%) and laboratory costs (8%). CONCLUSION. Cancer treatment incurs high costs, especially for end-of-life pharmaceutical expenses, ensued from medical personnel tendency to improve such patients' quality of life in spite of nearing the end of life. Reimbursement policy on monoclonal antibodies, in particular at end-stage disease, should rely on cost-effectiveness evidence as well as documented clinical efficiency