Cost-effectiveness Analysis of Denosumab in the Prevention of Skeletal-related Events in Patients with Prostate Cancer in Kazakhstan

Introduction. Bone mass loss (BML) is one of the adverse effects of oncological chemotherapy, especially in cases of hormonal types of cancer, such as a prostate cancer (PC). BML is strongly associated with skeletal-related events (SREs), therefore decreasing the quality of patient’s life. Denosumab shows an advantage over zoledronic acid (ZA) in delaying the first onset of SREs and subsequent SREs in adults with PC in several phase III clinical trials. Since generic ZA recently became available, the purpose of the present study was to assess the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with PC.Methods. A Markov model was constructed in Tree-Age Pro 2013 software program with 4-week model cycles to analyze the cost-effectiveness of the treatments from the perspective of Ministry of Health (MoH) over a 10-year PC cohort. Direct costs (in Kazakhstani monetary units “tenge” in 2014) included costs of drug, SRE (pathologic fracture, surgery to bone, radiation to bone, spinal cord compression), and adverse events treatment. All costs were discounted for 3% per year. Effectiveness was appraised based on the number of SREs. Health states were defined according to SRE occurrence, SRE history, and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model.Results. Over the 10-year period, denosumab incurred 103,091 tenge higher costs than brand ZA, 677,133 tenge higher costs than generic ZA, and 0.58 fewer SREs per patient with PC. The estimated incremental total direct costs per SRE avoided with the use of denosumab were 177,743 tenge (instead of brand ZA) and 1,167,470 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses.Conclusions.With the assumption that brand and generic ZAs are equally effective in the prevention of SREs in PC patients, denosumab seems to be a cost-effective alternative for brand ZA (insignificant difference in costs – less than 5%) and a costly alternative for generic ZA from the perspective of MoH of Kazakhstan

Study of the erythropoiesis activity of nano-encapsulated forms of erythropoietin

Introduction: The recombinant human erythropoietin (rhEPO) is used in the treatment of anemia. In order to improve its pharmacokinetic properties, nanoparticles of biodegradable polymers of natural or synthetic origin were used. The aim of this study was to investigate the effect of new nano-encapsulated forms of recombinant human erythropoietin for oral use on the erythropoiesis in the cyclophosphamide immunosuppression model.Material and methods: The CHOpE immortalized cells culture (a primary producer of rhEPO "Vector" in Russia) was used. The following biodegradable polymers were chosen: 0.05% and 0.005% carbopol, 0.05% and 0.005% kollidon, and 0.05% and 0.005% pectin. Immunosuppression was obtained by a single dose of i.p. injection of cyclophosphamide (250 mg/kg) in white mice (18-20 g). During the next 5 days, the nano-encapsulated erythropoietin (100 ED/mouse) was administered orally to each mouse. After 5 and 10 days, the cell count of the number of blood reticulocytes and the myelogram of bone marrow were performed. The control group of mice received injections of Eprex.Results: On the 5th day of the experiment, the highest level of reticulocyte was observed in the samples of erythropoietin with kollidon (0.05%) and pectin (0.005%) nanoparticles. On the 10th day, the highest activity was observed in the samples of erythropoietin substance with pectin at 0.05% and 0.005% concentrations. The levels of reticulocytes in these groups reached 13.53% and 14.55%, respectively. The results of the myelogram during immunosuppression showed some activity of erythropoietin in conjunction with both concentrations of pectin when a two-fold increase in the number of erythroblasts was observed on the 5th day. High degrees of erythrokaryocytes in the state of mitosis were observed in the 0.05% pectin samples. Similar results were observed in equivalent groups of control animals on the 10th day of the experiment, which is compatible with the data on Eprex action.Conclusion: The erythropoietic activity of nano-encapsulated forms of erythropoietin was observed in the 0.05% and 0.005% pectin samples in the cyclophosphamide immunosuppression model setting.

Removal of Cd2+ from water by use of super-macroporous cryogels and comparison to commercial adsorbents

In this study amphoteric cryogels were synthesized by the use of free-radical co-polymerization of acrylate-based precursors (methacrylic acid and 2-acrylamido-2-methyl-1-propansulfonic acid) with allylamine at different ratios. The physico-chemical characteristics of the cryogels were examined using SEM/EDX, FT-IR, XPS and zeta potential measurements. The cryogels were tested toward Cd 2+ removal from aqueous solutions at various pH and initial concentrations. Equilibrium studies revealed a maximum sorption capacity in the range of 132–249 mg/g. Leaching experiments indicated the stability of Cd 2+ in the cryogel structure. Based on kinetics, equilibrium and characterization results, possible removal mechanisms are proposed, indicating a combination of ion exchange and complexation of Cd 2+ with the cryogels’ surface functional groups. The cryogels were compared to commercially available adsorbents (zeolite Y and cation exchange resin) for the removal of Cd 2+ from various water matrices (ultrapure water, tap water and river water) and the results showed that, under the experimental conditions used, the cryogels can be more effective adsorbents

Polyphenol Concentrate from Kazakhstan Cabernet Sauvignon Collection of Grapes

Introduction. Nowadays, most of the research in the field of gerontology is focused on the effects of the grape polyphenols. In particular, resveratrol has been shown to increase life expectancy of various living organisms, including mammals. Resveratrol also plays an important role in cancer prevention and decreases the risk of developing cardiovascular disease. In our research, we proposed the development of the therapeutic product from Cabernet Sauvignon grapes that would exhibit the beneficial properties of polyphenols. Standard operating procedures were developed in our laboratories to collect alcohol free concentrate of polyphenols from the Kazakhstan Cabernet Sauvignon collection of grapes. The purpose of the study was to investigate the composition, biological safety, and potential therapeutic effects of the polyphenol concentrate.Methods. The total polyphenol amount was determined using the Enology Analyzer Y15 (BioSystems, Spain). HPLC analysis of the polyphenol composition was performed using Agilent 1290 chromatograph. The polyphenol concentrate was analyzed for the microbiological purity and the presence of the toxic elements. The cytoprotective effect of the polyphenol concentrate was studied in experimental models of diabetes, toxic hepatitis, doxorubicin cardiomyopathy, and acute radiation sickness.Results. The total polyphenol amount in one sample was 12,819 mg/l. Polyphenol composition analysis showed presence of the following polyphenols: catechin, epicatechin, gallic acid, quercetin, miricetin, 3-glucosylkaempferol, epicatechin gallate, 3-(3,4-Dihydroxyphenyl)-2-propenoic acid, catechin gallate, pitseid, kaempferol, n-hydroxy-cinnamic acid, resveratrol and chlorogenic acid. The concentrate was proven to be biologically safe and acceptable for use as a dietary supplement. The polyphenol concentrate demonstrated high antioxidant activity against ABTS and DPPH radicals in vitro. It also showed the following impacts on the various experimental models in vivo: reduction of sugar levels in diabetes; regeneration of the structure and function of the heart tissue in cardiomyopathy; regeneration of the nephron structure and function in nephropathy; regeneration of liver in toxic hepatitis; recovery of the antioxidant status in oxidative stress; and recovery of the hematopoiesis in acute radiation sickness.Conclusion. The polyphenol concentrate from Kazakhstan Cabernet Sauvignon collection of grapes was proved to be biologically safe and acceptable for use as a dietary supplement. The concentrate showed high antioxidant, antiradiation activity, and regenerative effect in diabetes, cardiomyopathy, nephropathy, and hepatitis in the corresponding organs.

Levels and distribution of self-rated health in the Kazakh population: results from the Kazakhstan household health survey 2012

The high and fluctuating mortality and rising health inequalities in post-Soviet countries have attracted considerable attention. However, there are very few individual-level data on distribution of health outcomes in Central Asian countries of the former Soviet Union. We analysed socioeconomic predictors of two self-rated health outcomes in a national survey in Kazakhstan

Therapeutic Potential of Noble Nanoparticles for Wound Repair

Introduction. Nanoparticles made of noble metals, such as gold and silver, have a great potential to be effectively employed for wound management. The nano-size of such particles provides an opportunity to enlarge the contacting area, which results in more effective anti-bacterial action and faster wound repair. It must be noted that the shape of noble nanoparticles might play a crucial role in the manifestation of their anti-microbial properties. The modern state of technology allows fabrication of the nanoparticles with the desired shape and physical properties. In order to provide efficacy and close contact with the wound, the noble nanoparticles can be incorporated into a special matrix made of a cryogel (based on polymethyl methacrylate). This combination might serve as a foundation for developing completely new types of wound dressing.Materials and methods. We have developed a few methods for synthesizing gold and silver nanoparticles of different shapes and sizes. After fabrication of metallic nanoparticles, they were characterized by using Tunneling Electron Microscopy (TEM) and Malvern Zetasizer system in order to determine the average population size and consistency. The silver nanoparticles was synthesized using sodium borohydride reduction of silver nitrate. The synthesis of gold nanoparticles was conducted by using the Turkevich method.Results. We have developed a synthetic cryogel based on polyacrylamide (by cryogelation reaction) at several temperatures. At the second step, we developed a method for conjugating fabricated gold and silver nanoparticles to the surface (or pores) of cryogel through covalent bonds so they can provide antibacterial action within the wound. By following the developed protocol, we were able to obtain an approximate cryogel layer (1 cm thickness) with embedded gold and silver nanoparticles. This conjugate was analyzed and confirmed using Scanning Electron Microscopy (SEM) and TEM.Discussion. The obtained results indicate the feasibility of the fabrication of a novel type of wound dressing. At the next step, we are planning to elucidate the bio-compatibility of the combination of cryogel and nanoparticles. Moreover, anti-bacterial properties of this new type of wound dressing will be analyzed.

Current state of chronic wound care in Kazakhstan: focus on topical treatments

Background — The presence of chronic hard-to-heal wounds significantly affects patients’ quality of life causing pain, discomfort, decrease of mobility and consequently leads to social isolation and depression. This type of wound is more prevalent among older population. It has been estimated that up to 1-2% of the world population have this condition. The treatment of hard-to-heal wounds is expensive and long-term process, and, stresses healthcare systems of every country. Unfortunately, limited information is available about the situation with chronic wounds in Kazakhstan as the statistical data on such patients is not monitored and not registered in this country. Methods — The search was conducted by using available electronic sources, including Google Scholar, PubMed, Web of Sciences, Medline, Wiley Online Library, and Cochrane Library databases as well as hard copy versions of peer-reviewed publications in Russian, Kazakh, and English languages. Results — We have identified and analyzed current situation with wound care in the Republic of Kazakhstan. Research has demonstrated a variety of types of treatments utilized in the country, particularly the treatment of the diabetic foot.It also indicates the lack of statistics on wound care. Conclusions — The review highlights the mechanisms of wound healing process, methods for wound care, and encompasses the information available on wound healing in Republic of Kazakhstan. The article emphasizes the necessity of establishing the systemic monitoring of wound care and formation of electronic database. Apart from that, the importance of developing and manufacturing of domestic novel wound treatments have been also stressed out

Development of new type of wound dressing based on cryogel matrix with incorporated nanoparticles

A cryogel (polymethyl methacrylate) has been chosen as a basis for new type of wound dressings, where incorporated silver and gold nanoparticles do provide effective antibacterial protection [1]. This function will be enhanced by extracorporeal application of microwave radiation in safe regime

New technology based on combination of cryogel and nanoparticles for wound management

The anti-microbial properties of noble metals have been known since ancient times. The new technology allows obtaining metal particles with programmed size and shape. Gold and silver nanoparticles have been employed for various bio-medical applications (1, 2, 3). In our study we developed the method of obtaining gold and silver nanoparticles with different shape. The nanoparticles are to be incorporated into the cryogel, which provides an ideal antimicrobial microenvironment for effective wound healing

A Comprehensive Review of Topical Odor-Controlling Treatment Options for Chronic Wounds: A Comprehensive Review

The process of wound healing is often accompanied by bacterial infection or critical colonization, resulting in protracted inflammation, delayed reepithelization, and production of pungent odors. The malodor produced by these wounds may lower health-related quality of life and produce psychological discomfort and social isolation