Pharmacoeconomic justification of the choice of specific therapy schemes for the treatment of adult patients with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive and debilitating disease that causes the blood vessels in the lungs to thicken and narrow, forcing the heart to pump blood through the lungs at high pressure. In recent years, a significant number of therapies have become available for the treatment of PAH. Pharmacoeconomic justification of the choice of specific pharmacotherapy requires weighing the effectiveness and cost of treatment of this disease and is extremely relevant. Given the limited budget for health care, the choice of drugs (drugs) should be based not only on the comparative clinical effectiveness of treatment, but also on the comparative cost-effectiveness, which ensures the maximum effectiveness of providing pharmaceutical care to patients with PAH. PAH is a life-threatening orphan disease with a poor prognosis, and in many cases a combination of specific drugs may be required regardless of their cost. Like patient survival, quality of life is the main factor in the pharmacoeconomic justification of the choice of specific drugs for the treatment of PAH. The objective of the paper – pharmacoeconomic research of specific therapy for the treatment of PAH and determination of «cost–utility», «quality of life», «QALY» indicators in various approaches to pharmacotherapy of PAH. The object of the study was the results of the analysis of pharmacotherapy schemes of patients with PAH in accordance with a certain functional class. Analytical, documentary, informational, graphic and mathematical research methods were used during the research. Our pharmacoeconomic analysis of the pharmacotherapy of patients with PAH who were in a certain functional class (FC) showed that for patients with FC II and FC III PAH, endothelin receptor antagonists (APE) or the combination of APE with prostaglandins was the least expensive treatment strategy and gave the largest average QALYs. At the same time, the obtained research results are the basis for the development of differential financing of PAH therapy for patients with different FCs. It should be noted that the study conducted by us is the first in Ukraine and can be the basis for further studies, strengthened by additional information and direct measurement of the impact of specific treatment on the quality of life of patients with the help of specially developed Ukrainian questionnaires, which can be used to estimate the increase in the QALY indicator during treatment, which will give a better idea about the effectiveness of these treatment methods

Scientific substantiation of the concept of pharmacoeconomic analysis of technologies for early diagnosis and pharmacotherapy of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery) for no apparent reason. Because symptoms are nonspecific and physical signs may be subtle, the disease is often diagnosed at late stages. Over the past few decades, significant progress has been made in the field of pulmonary arterial hypertension. Technological progress allows to diagnose the disease in the early stages, as well as to better assess the severity of the disease. Today, screening studies are becoming increasingly important to establish a clinical diagnosis and minimize lost opportunities without timely diagnosis, especially in patients with idiopathic PAH. Therefore, the issue of early diagnosis of patients with suspected PAH and confirmation of the diagnosis is a very important and urgent issue today. The objective of the paper: to study the methods of implementation of technologies for early diagnosis and pharmacotherapy of pulmonary arterial hypertension and conceptual presentation of the results of their implementation. The work used available scientific sources of information on the results of the implementation of diagnostic screening for early detection of PAH and pharmacotherapy in the world. The analysis of input data was carried out using systematic, documentary, informational and graphical research methods. The result of the analysis of information materials showed that over the past two decades, significant progress has been made in the treatment of PAH and more than doubled the survival rate of patients. It has been found that diagnostic screening is a relatively unique medical technology in relation to other medical interventions and can be defined as the systematic use of diagnostic technologies in individuals at risk to detect the disease before the onset of symptoms. The study proposes a systematic concept of economic evaluation of the diagnostic screening program for PAH to determine its optimal design. At the same time, this concept embodies the complex effect of the introduction of technologies for early diagnosis and pharmacotherapy of PAH, which is expressed in the positive dynamics of clinical indicators, reduced mortality and improved quality of life. It should be noted that a number of new tools and approaches for diagnostic screening give hope that advances in the diagnosis of PAH will also affect the effectiveness of medical care

Clinical characteristics of patients hospitalized to the Ukrainian expert-consultative center of pulmonary hypertension for adults

Pulmonary arterial hypertension (PAH) is a group of rare, malignant diseases that, without optimal treatment, quickly lead to death (the average survival of patients in the absence of specific therapy is 2.8 years from diagnosis). This nosology is most often diagnosed at an earlier age and mainly in female patients. The global trend indicates a predominance of PAH in women over men in 2–4 times greater. The objective of the paper to study the condition of inpatients to determine the strategy of medical care and identify ways to improve the pharmaceutical supply of patients with pulmonary arterial hypertension. The object of the study were the results of a retrospective analysis of medical records of inpatients 93 patients hospitalized at the Ukrainian Expert-Consultative Center for Pulmonary Hypertension for Adults, established on the basis of NSC «Strazhesko Institute of Cardiology of the National Academy of Medical Sciences of Ukraine». Analytical, documentary, informational, graphic and retrospective research methods were used during the research. According to the results of a retrospective analysis of 93 medical records of inpatients who were registered and treated at the Ukrainian Expert Advisory Center for Adults for the period from 2018 to 2021, it was found that almost all patients with PAH have heart problems and other concomitant pathological conditions. The period of inpatient treatment consisted of maintenance therapy with diuretics (spironolactone, furosemide, triphas, torside, torasemide), anticoagulants (warfarin), cardiac glycosides (digoxin) and iron supplements (maltoferfol) and specific therapies using calcium channel blockers (amlodipine), prostacyclin analogues (ventavis), endothelin receptor antagonists (bosentan) and phosphodiesterase type 5 inhibitors (sildenafil, no-lag). Patients with PAH were hospitalized for 2 days to 31 days, the average number of bed-days was 8.75 days per 1 patient. Thus, the results of the study of the clinical characteristics of patients hospitalized at the Ukrainian Expert Advisory Center of Pulmonary Hypertension for Adults, indicate the need to determine the technology of specific therapy of PAH with pharmacoeconomic analysis

Organization of pharmaceutical provision of patients with pulmonary hypertension on the example of Kyiv

In Ukraine, pharmaceutical provision of patients with pulmonary hypertension (PH) as a rare (orphan) disease is one of the important components of the State policy. Despite the permanent reform of the medical and pharmaceutical sector, a significant number of problems in the formation of a balanced system for providing the necessary medicinal products (MP) to orphan patients have not yet been resolved. The purpose of the study is to study the process of pharmaceutical provision of patients with PH, using the example of Kyiv. Information on MP purchases for patients in Kyiv, included in the Unified Clinical Protocol for Emergency, Primary, Secondary (Specialized) Medical Care Pulmonary Hypertension in Adults for the State and local budgets for 2018–2021, has been chosen as the object of the study. We have used system-review, documentary, and marketing research methods. The result of the analysis of the annual need for 2018–2021 in INN, necessary for the pharmaceutical provision of Kyiv patients with PH, has shown that the annual decrease in funding compared to 2018, namely: in 2019– by 17.54%, in 2020– by 32.52%, in 2021 – by 50.08%, due to a decrease in the cost of INN Sildenafil (Sildenafilum) by an average of 89.21% annually, compared with the cost in 2018. At the same time, the state of providing MP for patients with PH in Kyiv for the period 2018–2021 indicates that the total need for them was met at the expense of the State Budget of Ukraine and the budget of Kyiv for the implementation of the City Target Program «Health of Kievans» in 2018 – by 81.46%, and in 2019 – by 91.67% of the need. The supply of MP ordered for 2020 for the treatment of PH at the expense of the State Budget took place only at the end of 2021. Only Iloprost (Iloprostum) of the six supplies of INN ordered was completed, which accounted for 82.27% of the declared need. In 2021, only Sildenafil (Sildenafilum) was purchased at the expense of the State Budget of Ukraine, which is 8% of the need to provide treatment for patients with PH in the city of Kyiv. The City Target Program «Health of Kievans» for 2021 does not provide for expenses in the «Pulmonary Hypertension» direction. Thus, the results of a study of the organization of pharmaceutical support for Kyiv residents with PH indicate that there are no financial guarantees for the provision of free medical care to patients with rare (orphan) diseases

Complex prophylaxis of postoperative complications in colorectal surgery

Objective. To improve the immediate results of surgical treatment of colorectal cancer, using more effective prophylaxis of morbidity. Маterials and methods. The treatment efficacy of the Program of complex prophylaxis of postoperative complications in colorectal surgery, elaborated in the Clinic was studied up, using comparative analysis of the morbidity, occurred in 1253 patients, radically operated for cancer recti. In 2005 - 2010 yrs, when some elements of the elaborated Program have begun introduced into clinical practice, 361 patients were operated on (Group I). In 2011 - 2017 yrs, when the Program for prophylaxis of postoperative complications was applied in full volume, 892 patients, presenting the main group (Group II) were operated on. Results. Сomparative analysis of the elaborated program for complex prophylaxis of postoperative complications and of the «fast track» concept have shown several essential differences between them. Introduction of the Program elaborated into clinical practice have improved the immediate results of surgical treatment of cancer recti due to essential lowering of rate of different morbidities from 14.9 tо 9.2% and mortality - from 3.0 tо 1.8%. Conclusion. The Program for complex prophylaxis of postoperative complications in colorectal surgery, elaborated in the Clinic, guarantees the results improvement while surgical treatment of cancer recti and may be recommended for wide clinical application

Estimating and Forecasting the Resource-Ecological Security in the Context of Ensuring the Economic Security of Region

The article proposes methodical bases for forecasting of resource-ecological security in the context of development of ecological component of national economy. In particular, they include an adaptive model of estimating and forecasting the status of the resource-ecological security by means of the taxonomic analysis and the main components methods, indicative management, determination of factor loadings which impact security the most. The article also propose the system of supporting the decision-making for implementation of optimal management, realization of which allows to identify peculiarities and tendencies of development of the given sphere and to adjust financial flows, directed to financing of the nature-protective and resource efficient measures. The inverse relationship between the growth of economic security and the decline of resource-ecological security is determined, which indicates the raw-material orientation of the Ukrainian economy, gaining profit from the seizure of natural resources and deterioration of the quality of natural environment. Practical application of the developed approach is possible within the program-target method of management at development and realization of the State programs directed towards increase of stability both the resource-ecological security and the economic security of the State against the internal and external risks and threats

Dynamics of the north western coast of the azov sea

UA: Современная динамика склонов и побережья морей как отображение общего мобилизма литосферы, взаимодействия основных оболочек Земли под влиянием космических, планетарных, региональных и локальных факторов является актуальной научной и практической проблемой. В цепочке геолого-геоморфологических процессов склоновые гравитационные процессы являются наиболее активным звеном и непосредственно влияют на жизнедеятельность человека. В свою очередь, хозяйственная деятельность человека вносит существенные изменения в процесс эволюции геологической среды, в том числе в характер протекания склоновых процессов. EN: Development of slope gravity processes on the coast of the Sea of Azov is a serious environmental and geological problem and requires topical engineering and geological research and solutions. Slope gravitational processes adversely affect the state of the soil layer, causing erosion and washing away of soils, contribute to siltation and contamination of water bodies. Movements on the slopes cause destruction of economic objects, residential buildings, loss of agricultural land. To prevent the negative consequences of slope processes, their deep and systematic study is necessary

The impact of financial digitalization on ensuring the economic security of a country at war: New measurement vectors

The military actions in Ukraine have actualized the transformation and revision of existing approaches to assessing the country’s economic security. Financial security, which is considered in this paper through its standard components such as financial sector security, stock market security, debt and budget security, has a significant effect on the formation of economic security. At the same time, digitalization in the financial sector was identified as a new component that provides access to financial resources even in the context of the deployment of hostilities in Ukraine. Therefore, this study assessed the effect of the state of financial security, taking into account the importance of financial digitalization for the economic security of Ukraine. Based on quarterly data for the period 2015–2021, 42 indicators were analyzed, which were grouped according to the relevant components of financial security, and their integral indicators were determined using the Harrington method. A factor analysis of the formation of economic security was carried out using the principal components analysis, and an integral indicator of a country’s economic security was calculated based on the Kinney multiplicative convolution. The integral indicator of economic security for 2025– 2021 doubled and amounted to 0.63 units, which was due to the increased influence of financial digitalization processes, all other components either slowly decreased or were stable. Thus, the reserve of economic security that was formed during this period, including due to the intensive digitalization of the financial sector, allowed Ukraine to survive the first weeks of the war and ensure the functioning of the financial system

M153R Mutation in a pH-Sensitive Green Fluorescent Protein Stabilizes Its Fusion Proteins

BACKGROUND: Green fluorescent protein (GFP) and its fusion proteins have been used extensively to monitor and analyze a wide range of biological processes. However, proteolytic cleavage often removes GFP from its fusion proteins, not only causing a poor signal-to-noise ratio of the fluorescent images but also leading to wrong interpretations. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the M153R mutation in a ratiometric pH-sensitive GFP, pHluorin, significantly stabilizes its fusion products while the mutant protein still retaining a marked pH dependence of 410/470 nm excitation ratio of fluorescence intensity. The M153R mutation increases the brightness in vivo but does not affect the 410/470-nm excitation ratios at various pH values. CONCLUSIONS/SIGNIFICANCE: Since the pHluorin(M153R) probe can be directly fused to the target proteins, we suggest that it will be a potentially powerful tool for the measurement of local pH in living cells as well as for the analysis of subcellular localization of target proteins

Co-production of hydrogen and ethanol from glucose in Escherichia coli by activation of pentose-phosphate pathway through deletion of phosphoglucose isomerase (pgi) and overexpression of glucose-6-phosphate dehydrogenase (zwf) and 6-phosphogluconate dehydrogenase (gnd)

Background: Biologically, hydrogen (H-2) can be produced through dark fermentation and photofermentation. Dark fermentation is fast in rate and simple in reactor design, but H-2 production yield is unsatisfactorily low as < 4 mol H-2/ mol glucose. To address this challenge, simultaneous production of H-2 and ethanol has been suggested. Co-production of ethanol andH(2) requires enhanced formation of NAD(P) H during catabolism of glucose, which can be accomplished by diversion of glycolytic flux from the Embden-Meyerh-of-Parnas (EMP) pathway to the pentose-phosphate (PP) pathway in Escherichia coli. However, the disruption of pgi (phosphoglucose isomerase) for complete diversion of carbon flux to the PP pathway made E. coli unable to grow on glucose under anaerobic condition. Results: Here, we demonstrate that, when glucose-6-phosphate dehydrogenase (Zwf) and 6-phosphogluconate dehydrogenase (Gnd), two major enzymes of the PP pathway, are homologously overexpressed, E. coli.pgi can recover its anaerobic growth capability on glucose. Further, with additional deletions of Delta hycA,Delta hyaAB,Delta hybBC,Delta ldhA, and Delta frdAB, the recombinant.pgi mutant could produce 1.69 mol H-2 and 1.50 mol ethanol from 1 mol glucose. However, acetate was produced at 0.18 mol mol(-1) glucose, indicating that some carbon is metabolized through the Entner-Doudoroff (ED) pathway. To further improve the flux via the PP pathway, heterologous zwf and gnd from Leuconostoc mesenteroides and Gluconobacter oxydans, respectively, which are less inhibited by NADPH, were overexpressed. The new recombinant produced more ethanol at 1.62 mol mol(-1) glucose along with 1.74 mol H-2 mol(-1) glucose, which are close to the theoretically maximal yields, 1.67 mol mol(-1) each for ethanol andH(2). However, the attempt to delete the ED pathway in the.pgi mutant to operate the PP pathway as the sole glycolytic route, was unsuccessful. Conclusions: By deletion of pgi and overexpression of heterologous zwf and gnd in E. coli Delta hycA Delta hyaAB Delta hybBC Delta ldhA Delta frdAB, two important biofuels, ethanol andH(2), could be successfully co-produced at high yields close to their theoretical maximums. The strains developed in this study should be applicable for the production of other biofuels and biochemicals, which requires supply of excessive reducing power under anaerobic conditions