Do Health Reforms Impact Cost Consciousness of Health Care Professionals? Results from a Nation-Wide Survey in the Balkans.

BACKGROUND: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician's mindsets and decision-making in practice. AIMS: Assessment of healthcare professionals' judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. STUDY DESIGN: Cross-sectional study. METHODS: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire-29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician's attitudes on: Clinical-Decision-Making-between-Alternative-Interventions (CDMAI), Quality-of-Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. RESULTS: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). The surgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. CONCLUSION: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making were modest. Clinicians' perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians' cost consciousness.

Factors influencing antibiotic treatment cost and outcome in critically ill patients: a "real-life" study.

UNLABELLED: BACKGROUND/AIM. Critically ill patients are at very high risk of developing severe infections in intensive care units (ICUs). Procalcitonin (PCT) levels are eleveted in the circulation in patients with bacterial sepsis and PCT might be useful in guiding antibiotic treatment. The aim of this study was to estimate factors influencing patients survival and treatment cost in ICU with special emphasis on the impact of PCT serum levels use in guiding antimicrobial therapy. METHODS: The study was conducted from August 2010 to May 2012 in the Intensive Therapy Unit, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy (MMA), Belgrade, Serbia. All adult critically ill patients with sepsis and/or trauma admitted in the ICU were included in the study. This study included only the cost of antimicrobial therapy in the ICU and the cost for PCT analysis. We used prices valid in the MMA for the year 2012. PCT in serum was measured by homogeneous immunoassay on a Brahms Kryptor analyzer. RESULTS: A total of 102 patients were enrolled. The mean patients age was 55 ± 19 years and 61.8% of patients were male. The mean length of stay (LOS) in the ICU was 12 ± 21 days. There was a statistically significant difference (p < 0.001) between the sepsis and trauma group regarding outcome (higher mortality rate was in the sepsis group, particularly in the patients with peritonitis who were mostly women). The patients younger than 70 years had better chance of survival. LOS, the use of carbapenems and PCT-measurement influenced the cost of therapy in the ICU. CONCLUSIONS: The obtained results show that age, the diagnosis and gender were the main predictors of survival of critically ill patients in the ICU. The cost of ICU stay was dependent on LOS, use of carbapenems and PCT-measurement although the influence of these three factors on the outcome in the patients did not reach a statistical significance.

Quality assessment of total parenteral nutrition admixtures by the use of fractional factorial design.

BACKGROUND/AIM: Parenteral nutrition as a specific as pect of providing nutritients still remains a permanent topic of both theoretical and experimental research. Total parenteral nutrition (TPN) admixtures have complex con tents making difficult to maintain their stability. The most critical parameter is the diameter of a lipid droplet, i.e. droplet size distribution. It is recommended that droplet size should not be more than 5 microm and that the presence of greater droplets should not exceede the value of 0.05%. Lipid droplets size is affected particularly by electrolyte addition, especially polyvalent cations. There is a danger of the added electrolytes interaction with lipid droplets which leads to their aggregation and negative effects upon the admixtures stability. The aim of this study was to as sess the effect of added electrolyte and lipid phase quan tity on the admixture stability. METHODS: Electrolytes were added to the studied admixture of a defined basic formulation contents in accordance with recommenda tions from the literature. Droplets size measurements were performed using the method of laser diffraction with a laser particles analyzer. Effects of independent variables were calculated and evaluated using commercial software. Na(+), K(+), Ca(2+) and Mg(2+) concentrations, as well as the quantity of fat phase were chosen as studied fac tors, i.e. independed variables. The system response, or dependent variable was the median of droplets size. Each of the factors was varied at two levels, higher (+1) and lower (-1), according to the 2(5-2) fractional factorial design. RESULTS: The study suggested the presence of relative uni formity of the results of all the measurements regardless of the quantity of added electrolytes and lipid phase. It was shown that undoubtedly there is the influence of 2 valent cations (calcium and magnesium) upon lipid drop lets size, which is in a direct correlation with theoretical assumption. CONCLUSION: Within a 72-hour testing period there was no significant increase in droplet size, i.e. the studied admixtures remained stable considering droplet size median as the criterion of stability.

Effect of pretreatment with omega-3 polyunsaturated fatty acids (PUfas) on hematological parameters and platelets aggregation in patients during elective coronary artery bypass grafting.

BACKGROUND/AIM: [corrected] Using omega-3 polyunsaturated fatty acids (PUFAs) in coronary artery bypass graft surgery (CABG) could provide protection against ischemic-reperfusion damage, prevention of postoperative arrhyth mia and attenuation of inflammatory response. However, omega-3 PUFAs inhibit cyclooxygenase (and thus decrease the synthesis of thromboxane A2 from arachidonic acid in platelets), which leads to decreased platelet aggregation. In cardiac surgery it is necessary to achieve a balance between inhibition and full platelets function. It is as well as im portant to closely follow hematological parameters, im paired by CABG itself. Therefore, the aim of the study was to establish the effects of pretreatment with omega-PUFAs on hematological parameters and plateletes aggre gation in patients with elective CABG. METHODS: This prospective, randomized, placebo-controlled, single-center trial was performed on parallel groups. The patients (n = 40) undergoing elective CABG were randomized receivin preoperative intravenous omega-3 PUFAs (Omegaven 10%) infusion (the PUFAs group) or the same volume of 0.9% saline solution infusion (the control group). Infusion was given a day before surgery and repeated four hours before starting extracorporeal circulation (CPB) via the pe ripheral vein at single doses of 100 mL (25 mL/h). Platelet function analysis was performed using multiple electrode aggregometry (MEA, multiplate-analyzer) before starting CPB and 2 h postoperatively for the patients of both groups. Results. There were no clinically relevant differ ences in baseline characteristics between the groups. He matological parameters were not significantly different between the groups pre-, intra- and postoperatively. Dur ing the first 24 h after surgery, the loss of blood was simi lar in the PUFAs and the control group (680 +/- 274 mL and 608 +/- 210 mL, respectively; p = 0.356). Postopera tively, platelet aggregation was not significantly different between the PUFAs and the control group in adenosine diphosphate (ADP) test (39 +/- 11 and 42 +/- 15, respec tively; p = 0.701), arachidonic acid (ASPI) test (64 +/- 24 and 70 +/- 27, respectively; p = 0.525) and trombin receptor-activating peptide (TRAP) test (68 +/- 25 and 75 + 26, respectively; p = 0.396), while their aggregation in collagen (COL) test was statistically significantly lower in the PUFAs related to the control group (32 +/- 15 and 47 +/- 20, re spectively; p = 0.009). Conclusion. Acute pretreatment with omega-3 PUFAs insignificantly affected the activity of platelets and did not influence postoperative blood loss.

Myocardial protection during elective coronary artery bypasses grafting by pretreatment with omega-3 polyunsaturated fatty acids.

BACKGROUND/AIM: Despite recent advances in coronary artery bypass grafting (CABG), cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) are still associated with myocardial injury. Accordingly, the efforts have been made lately to improve the outcome of CPB by glucose-insulin-potassium, adenosine, Ca(2+)-channel antagonists, L-arginine, N-acetylcysteine, coenzyme Q10, diazoxide, Na+/H+ exchange inhibitors, but with an unequal results. Since omega-3 polyunsatutated fatty acids (PUFAs) have shown remarkable cardioprotection in preclinical researches, the aim of our study was to check their effects in prevention of ischemia reperfusion injury in patients with CPB. METHODS: This prospective, randomized, placebo-controlled study was performed with parallel groups. The patients undergoing elective CABG were randomized to receive preoperative intravenous omega-3 PUFAs infusion (n = 20) or the same volume of 0.9% saline solution infusion (n = 20). Blood samples were collected simultaneously from the radial artery and the coronary sinus before starting CPB and at 10, 20 and 30 min after the release of the aortic cross clamp. Lactate extraction/excretion and myocardial oxygen extraction were calculated and compared between the two groups. The levels of troponin I (TnT) and creatine kinase-myocardial band (CK-MB) were determined before starting CPB and 4 and 24 h postoperatively. RESULTS: Demographic and operative characteristics, including CPB and aortic cross-clamp time, were similar between the two groups of patients. The level of lactate extraction 10 and 20 min after aortic cross-clamp time has shown negative values in the control group, but positive values in the PUFAs group with statistically significant differences (-19.6% vs 7.9%; p < 0.0001 and -19.9% vs 8.2%; p < 0.0008, respectively). The level of lactate extraction 30 minutes after reperfusion was not statistically different between the two groups (6.9% vs 4.2%; p < 0.54). Oxygen extraction in the PUFAs group was statistically significantly higher compared to the control group after 10, 20 and 30 min of reperfusion (35.5% vs 50.4%, p < 0.0004; 25.8 % vs 48.7%, p < 0.0001 and 25.8% vs 45.6%, p < 0.0002, respectively). The level of TnT, 4 and 24 h after CPB, was significantly higher in the control group compared to PUFAs group, with statistically significant differences (11.4 vs 6.6, p < 0.009 and 12.7 vs 5.9, p < 0.008, respectively). The level of CK-MB, 4 h after CPB, was significantly higher in the control group compared to PUFAs group (61.9 vs 37.7, p < 0.008), but its level, 24 h after CPB, was not statistically different between the two groups (58.9 vs 40.6, p < 0.051). CONCLUSION: Treatment with omega-3 PUFAs administered preoperatively promoted early metabolic recovery of the heart after elective CABG and improved myocardial protection. This study showed that omega-3 emulsion should not be considered only as a nutritional supplement but also as a clinically safe and potent cardioprotective adjunct during CPB.

Are COX-2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?

RATIONALE: In developed countries, cyclooxygenase 2 (COX-2) inhibitors were shown to be less costly than the combination of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in treatment of patients with high risk of serious gastrointestinal (GI) adverse effects. It is questionable if such results apply to developing countries where health service costs are lower and there is high discrepancy between generic and patent protected drug prices. We analysed the direct cost of treatment with generic NSAIDs in combination with PPIs versus branded COX-2 inhibitors in patients with high risk of serious GI adverse effects from the perspective of the public health service in Serbia. METHODS: Total cost of treatment of serious GI complications and the use of NSAID+PPI versus COX-2 inhibitors were calculated. A model for estimation of cost of treatment of NSAID+PPI versus COX-2 inhibitors which included the probability of developing serious GI adverse effects was developed. RESULTS: Total cost of treatment of serious GI adverse effects resulted in an average of $814/patient. Considering the relative risk of such adverse effects for patients with four or more risk factors, the least costly treatment over 6 months was the use of celecoxib ($487). Compared with diclofenac+omeprazole, cost savings were estimated at $59 and $22 per patient with celecoxib and etoricoxib, respectively. CONCLUSION: Cost savings may be achieved by using COX-2 inhibitors in patients at high risk of GI adverse effects even in countries with moderate health care service expenditures. Such possibility requires further investigation.

[Preparation and testing of solutions for organ perfusion and preservation in transplantation].

BACKGROUND/AIM: Histidine-tryptophan-ketoglutarate (HTK) solution is the most frequently used solution for the preservation of abdominal organs by leading transplant centers worldwide. The aim of the study was to investigate whether it is possible to prepare this kind of perfusion solution in the hospital pharmacy. In the hospital pharmacy setting we prepared HTK preservation solution and tested its quality, and in accordance with the obtained results recommended its shelf-life. METHODS: A multicomponent HTK solution was prepared following standardized aseptic procedures for sterile products. Components of HTK solution were dissolved in water for injection under aseptic conditions and the obtained solution was sterilized by bacteriological membrane filtration (0.22 microm). The quality of the produced solution was examined using physical and physico-chemical methods and biological tests. Following pharmacopoeial regulations, we examined clarity, pH value, sterility and performed testing on pyrogens. The content of the amino acids histidine and triptophan was determined by using high pressure liquid chromatography (HPLC) method. The concentrations of chloride ions were investigated by retitration method. Atomic absorption spectrometry and ion-exchange chromatography with conductometric detection were used for determining the level of magnesium and calcium ions and the concentrations of sodium and potassium ions in HTK solution, respectively. RESULT: It was shown that the quality of the prepared HTK solution complied with the regulation demands. Also, pH value of the solution as a function of storage temperature, remained in the physiological range (pH 7.4). CONCLUSION: According to the obtained results of physico-chemical and biological testing it can be concluded that in the hospital pharmacy setting with the applied technological procedure, we can produce HTK preservation solution of the required quality. Keeping of HTK preservation solution in a refrigerator at 4 degrees C warrants its shelf-life of six months.

[Stability investigation of total parenteral nutrition admixture prepared in a hospital pharmacy].

BACKGROUND/AIM: In the cases when nutrition of patients can not be orally nor enterally performed, parenteral nutrition is a method of the therapy that provides more successful and rapid recovery. In that way, hospitalization can be significantly shorter, healing costs reduced and mortality minimized. Total parenteral nutrition (TPN) admixtures are the most complex systems which contain amino acids, carbohydrates, lipid emulsion, macroelectrolytes (Na+, K+, Ca2+, Mg2+, Cl(-), SO4(2-), PO4(3-)), oligoelements, hydro- and liposoluble vitamines, heparin, insulin and water. Concerning the mentioned complexity, special attention should be payed to physicochemical and microbiological stability of a mixture, because of interactions among components, that can be very hard to analyze. The aim of this study was to investigate the problem of stability of TPN admixtures prepared in a hospital pharmacy. METHODS: Admixture TPN was aseptically prepared in laminar air--flow environment on the basis of the specified order in supplementing components and additives to basic solutions. Solutions were kept in sterile multicompartment ethylene-vinyl-acetate bags. After preparation and slow homogenization, TPN admixtures were submitted to physicochemical and microbiological stability analyses in various period of time. The assessment of physical stability of TPN admixture was done on the basis of visual inspection, determination of pH value and measuring of particle size. The investigation of sterility and pyrogenic test were performed according to Ph. Yug. V regulations. RESULTS: Physico-chemical and microbiological analyses were applied and no significant changes in visual sense, pH value and droplet size stability of the TPN admixture were observed during the period of 60 hours The lipid droplets were smaller in size than 5 microm, that is the most common pharmacopoeia requirement. CONCLUSION: The results of our study confirmed that a TPN admixture prepared in a hospital pharmacy can be stored without stability loss for at least 60 hours.

Evaluation of the immunomodulatory activities of royal jelly components in vitro.

In this work the effect of different components isolated from royal jelly (RJ) was studied using an in vitro rat T-cell proliferation assay. We found that lower concentrations of MEL 174 (final water extract of RJ) and MEL 147 (3-10-dihydroxydecanoic acid) stimulated T-cell proliferation, triggered by concanavalin A (Con-A) and the process was followed by an increase in the production of interleukin-2 (IL-2). Higher concentrations of MEL 174, MEL 247 (dry powder of RJ) and MEL 138 (trans-10-hydroxydec-2-enoic acid) inhibited T-cell proliferation. The inhibition of T-cell proliferation in the presence of MEL 174 was followed by a decrease in IL-2 production, which was partly abrogated by exogenous IL-2, a decrease in nitric oxide (NO) production and increased apoptosis. In conclusion, our results showed the complexity of biological activity of RJ and suggest that its water extract possesses the most potent immunomodulatory activity in vitro.

[Preparation and testing of buffered eye drops containing pilocarpine chloride with timolol maleate].

BACKGROUND/AIM: In glaucoma therapy beta-blocator, timolol-maleate, is the first-line medicine of selection, whereas a miotic, pilocarpine chloride, is one of the oldest medicines used for the treatment of this illness. They are applied as eye drops. In order to achieve a better therapeutic effect and improve life quality of the ill, we produced and tested eye drops formulations based on combining pilocarpinechloride and timolol maleate in buffers of diferent pH values. METHODS: Following the general pharmacopoeial eye drops preparation regulation, we prepared formulations, of solution type, of pilocarpine chloride and timolol maleate combination, of pilocarpine choloride alone and of timolol maleate alone. A modified phosphate buffer according to Sorensen at 7.4, 7.7 and 8.0 pH values was used as a solvent. The quality of the produced formulations was examined using physical and physico-chemical methods and biological tests. Following pharmacopoeial regulations, we examined clarity, pH value and sterilty. Pilocarpine chloride level was determined by means of ion-par (High Performance Liguid Chromatography) RP-HPLC method, whereas UV/VIS absorption spectrophotometry was used for determining the level of both timolol maleate, and timolol. RESULTS: Results showed that monocomponent and combined preparations complied with the regulation demands. With the increase in the pH value of the solution pilocarpine chloride level decreased in relation to its initial content, whereas timolol level showed a tendency of moderate increase. CONCLUSION: Magistrally prepared pilocarpine chloride eye drops with timolol maleate have satisfied all the required conditions for an ophtalmological preparation. A modified phosphate buffer according to Sorensen at 7.4 pH value proved to be the most optimal solvent.