Dostupnost lekova za retke bolesti - komparativna analiza legislativnih zahteva između Srbije, Hrvatske i Makedonije

Access to orphan drugs (In EU regulation Orphan Drugs are referred as Orphan Medicinal Products (OMP)) is a key role in determining whether patients with rare diseases (RDs) will receive adequate and efficient treatment. The objective of this article is to identify differences in patient access to orphan drugs in 3 pharmaceutical markets: Serbia, Croatia and Macedonia. Patient access was defined: as the market access (availability) and affordability (financial accessibility). We analysed the legislative requirements for the authorisation process and made a cross country comparison. Retrospective cross-sectional analysis was done on drug lists in selected countries and a cross-comparison between the List of Orphan Drugs in Europe (LODE) for a six-month period (May 2014-October 2014). We included all 179 OMPs marketed in EU in our analysis, which had received market authorization in Croatia upon its membership in the EU. Total number of marketed drugs in Serbia was 59 (32.96%) drugs and in Macedonia 52 (29.05%) drugs. However, market authorization does not guarantee patient access to any given drug, so only 39.11% of OMPs could be accessed by Croatian patients (70 drugs).The number of refunded drugs in Serbia and Macedonia was smaller (32 and 20, respectively) which makes respectively, 17.88% and 11.17% of drugs on the LODE. The present study showed some variations between countries in selected indicators of availability and access to orphan drugs. Patients in Croatia had greater number of registered and refunded drugs, but in Serbia more than a half of registered OMPs could be refunded from National Health Insurance Fund. Macedonia had smaller number of inhabitants and also had the smaller number of patients from certain RDs which results in lower total number of OMPs.Dostupnost lekova za retke bolesti (orfan lekovi, u EU regulativi koristi se izraz na engleskom Orphan medicinal products, OMP) igra važnu ulogu u tome da li će bolesnici sa retkim bolestima imati pristup efikasnoj i adekvatnoj terapiji. Ciljevi ovog rada su da se identifikuju razlike u pristupu bolesnika orfan lekovima u tri odabrane zemlje: Srbiji, Hrvatskoj i Makedoniji. Pristup orfan lekovima definisana je kao: tržišna pristupačnost (dostupnost) i priuštivost (finansijska pristupačnost). Analizirali smo legislativne zahteve u procesu stavljanja leka u promet i uradili komparaciju među posmatranim zemljama. Retrospektivnom studijom preseka poredili smo nacionalne liste lekova posmatranih zemalja i Listu orfan lekova u EU, za period od šest meseci (maj-oktobar 2014.). Od ukupno 179 OMP, koliko ih je u tom periodu bilo sa dozvolom za stavljanje u promet u EU, u Srbiji je bilo registrovano 59 (32,96%), u Makedoniji 52 (29,05%), dok su u Hrvatskoj učlanjenjem u EU svi registrovani lekovi postali tržišno dostupni. Međutim, dozvola za stavljanje u promet nije i garancija da bolesnik ima pristup datom leku, pa je samo 39,11% lekova sa dozvolom za stavljanje u promet bilo na listi lekova koje se refundiraju u Hrvatskoj (70 OMP). Broj lekova kojima bolesnici imaju pristup preko nacionalnih fondova zdravstvenog osiguranja u Srbiji i Makedoniji su manji (32 OMP i 20OMP, respektivno), što čini da je priuštivost lekova u Srbiji tek 17,88% , a u Makedoniji 11,17% od liste orfan lekova u EU. Broj lekova, fizička i finansijska pristupačnost u analiziranim zemljama nije ista, dok je u Hrvatskoj bolesnicima dostupan najveći broj registrovanih lekova, u Srbiji se više od polovine registrovanih OMP može refundirati o trošku RFZO. Makedonija zbog manjeg broja stanovnika ima manji broj obolelih od RB, što rezultira manjim brojem OMP

Числено изследване на химически реакции чрез Monte Carlo симулация

Добри Данков, Владимир Русинов, Мария Велинова, Жасмина Петрова - Изследвана е химическа реакция чрез два начина за моделиране на вероятността за химическа реакция използвайки Direct Simulation Monte Carlo метод. Изследван е порядъка на разликите при температурите и концентрациите чрез тези начини. Когато активността на химическата реакция намалява, намаляват и разликите между концентрациите и температурите получени по двата начина. Ключови думи: Механика на флуидите, Кинетична теория, Разреден газ, DSMCThis paper presents numerical results for chemical reaction simulation with Direct Simulation Monte Carlo method using two different reaction probability models. The order of differences in the temperatures and the concentrations are studied by these ways. When the chemical reaction activity decreases, then the differences between the concentrations and the temperatures obtained by the two ways decrease. *2000 Mathematics Subject Classification: 65C20.This work is supported by the NSF of Bulgaria under Grant No DID 02/20 – 2009

Density Functional Theory Assessment of the Environment Polarity Effect on Polyaniline–Water Coupling

Crystallization water plays an important role in the self-organization of oligomer chains in conducting polyaniline. In order to quantify the interaction between emeraldine salt and such a water, models containing a tetramer in bipolaronic or polaronic form, chloride counterions, and an explicit water molecule are used. Different initial positions of water with respect to the oligomer chaintangential and verticalare considered. Various media are simulated by introducing an implicit solvent continuum of decreasing polarity. The DFT-D3/PCM computational approach is employed to examine the behavior of the systems in several aspectsthe role of the explicit water position and the effect of the environment polarity on the spatial structure, energetics, charge distribution, and the frontier molecular orbital energies. The strength of hydrogen bonding and the patterns of charge redistribution invoked by the water molecule are discussed. The study establishes trend lines in the variation of the molecular characteristics upon change of milieu as a tool for control of the self-assembly process. The results show that chains interact more efficiently with tangentially placed water. The influence of the environment polarity is minor and is mainly expressed in slight shortening of the intermolecular distances and mild decrease of the group charges of the system components with reduction of polarity

Absorption Spectra of Model Single Chains of Conducting Polyaniline

The theoretical study addresses the type and nature of the transitions in the absorption spectra of octamers, dodecamers, and hexadecamers of the emeraldine saltthe conducting form of polyaniline. Each of the fully protonated oligomers is modeled in its lowest singlet (bipolaronic form) and highest possible multiplicity (polaronic form). Two configurations of the chloride counterions with respect to the oligomer chains are considered. All structures are optimized with BLYP/6-31G*/PCM, while the spectra are evaluated with CIS/6-31G*/PCM. The optical behavior of the bipolaronic and polaronic forms of the investigated systems is discussed and compared to relevant experimental data. The optical transitions at about 400 and 800 nm characteristic for the emeraldine salt are registered for all model structures. Weighed against experimental and earlier theoretical findings the results prove that CIS gives qualitatively correct electronic spectra of these conjugated species. While the two configurations have almost identical spectra in the highest multiplicity, the singlets’ absorption conduct turns out to be sensitive to the counterions position. In all cases the most intensive absorption is the longest wavelength one in the near-IR region, but the number and oscillator strengths of the polaronic and bipolaronic bands are noticeably dissimilar. The bands of the low-spin oligomers are grouped, while those of the high-spin species cover the entire visible region. Each extension of the chain with one elementary unit contributes systematically a set of new bands to the spectrum. The possibility for a solvatochromic effect is estimated

REVIEWING TRANSFERABILITY IN ECONOMIC EVALUATIONS ORIGINATING FROM EASTERN EUROPE

Objectives: The aim of this study is to analyze the quality and transferability issues reported in published peer-reviewed English-language economic evaluations based in healthcare settings of the Central and Eastern European (CEE) and former Soviet countries. Methods: A systematic search of economic evaluations of healthcare interventions was performed for Armenia, Azerbaijan, Belarus, Bulgaria, Estonia, Georgia, Turkmenistan, Kazakhstan, Lithuania, the former Yugoslav Republic of Macedonia, Republic of Moldova, Romania, the Russian Federation, Serbia, Slovenia, and Ukraine. The included studies were assessed according to their characteristics, quality (using Drummond's checklist), use of local data, and the transferability of inputs and results, if addressed. Results: Most of the thirty-four economic evaluations identified were conducted from a healthcare or payer perspective (74 percent), with 47 percent of studies focusing on infectious diseases. The least frequently and transparently addressed parameters were the items’ stated perspectives, relevant costs included, accurately measured costs in appropriate units, outcomes and costs credibly valued, and uncertainties addressed. Local data were often used to assess unit costs, baseline risk, and resource usage, while jurisdiction-specific utilities were included in only one study. Only 32 percent of relevant studies discussed the limitations of using foreign data, and 36 percent of studies discussed the transferability of their own study results to other jurisdictions. Conclusions: Transferability of the results is not sufficiently discussed in published economic evaluations. To simplify the transferability of studies to other jurisdictions, the following should be comprehensively addressed: uncertainty, impact of influential parameters, and data transferability. The transparency of reporting should be improved

Pharmacist's Perspectives on Administering a COVID-19 Vaccine in Community Pharmacies in Four Balkan Countries

Community pharmacists expanded their roles and engaged in vaccination services in many countries around the world, but not in Balkan countries. This research aimed to assess the perceptions of pharmacists on involvement in the coronavirus disease (COVID-19) vaccine administration in four Balkan countries (Albania, Bulgaria, Romania, and Serbia). A cross-sectional survey was conducted using an online questionnaire that was distributed to community pharmacists across these countries between February and March 2021. A total of 636 community pharmacists were included in the analysis of the survey. The willingness to administer vaccines for COVID-19 (or other vaccines well established in the practice, like a flu vaccine) in community pharmacies is significantly different among the countries: the pharmacists from Albania were more willing to administer vaccines. The factors associated with the eagerness to vaccinate are almost the same among the countries: the lack of training in the faculty classes and the lack of a special place where to administer vaccines. Additional significant factors were found in Bulgaria (pharmacists from independent pharmacies wanted more than the pharmacists working in chain pharmacies to administer vaccines) and in Serbia (male pharmacists agreed more with administering vaccines than female pharmacists). Further national reforms are needed for adopting the expanding role of community pharmacists

Surface Functionalization of Exosomes Using Click Chemistry

A method for conjugation of ligands to the surface of exosomes was developed using click chemistry. Copper-catalyzed azide alkyne cycloaddition (click chemistry) is ideal for biocojugation of small molecules and macromolecules to the surface of exosomes, due to fast reaction times, high specificity, and compatibility in aqueous buffers. Exosomes cross-linked with alkyne groups using carbodiimide chemistry were conjugated to a model azide, azide-fluor 545. Conjugation had no effect on the size of exosomes, nor was there any change in the extent of exosome adherence/internalization with recipient cells, suggesting the reaction conditions were mild on exosome structure and function. We further investigated the extent of exosomal protein modification with alkyne groups. Using liposomes with surface alkyne groups of a similar size and concentration to exosomes, we estimated that approximately 1.5 alkyne groups were present for every 150 kDa of exosomal protein