Analysis of the cost-effectiveness of early diagnosis and pharmacotherapy of pulmonary arterial hypertension

Over the past decades, health policy makers have focused on early diagnosis to introduce targeted and innovative treatments. Early diagnosis of pulmonary arterial hypertension (PAH) is associated with improved long-term survival, so screening high-risk groups is a reasonable strategy to improve outcomes in PAH treatment. Today, screening is an important part of preventive medicine, with the goal of detecting disease at an early and pre-symptomatic stage. All healthcare systems have limited resources and face opportunity costs; this means that any investment in a screening tool will come at the expense of other healthcare services, to the detriment of those patients who would otherwise be treated. By recognizing opportunity costs, health systems can require that health interventions be both clinically and cost-effective to be considered for implementation. The objective of the paper –to conduct a cost-effectiveness analysis of early diagnosis and pharmacotherapy of pulmonary arterial hypertension. Our analysis of the cost-effectiveness of early diagnosis and pharmacotherapy of pulmonary arterial hypertension is based on a cost‒utility model that estimates patient survival, which is significantly improved by reducing the delay in diagnosis of PAH and indicates the prevention of premature death of undiagnosed patients. The analysis of input data was conducted using systematic review, documentary, informational and graphical research methods. The results of the study showed that the choice of the target population and the level of diagnostic coverage of this risk group is critical for the cost-effectiveness of the implementation of PAH diagnostic screening. A decrease in these indicators leads to a decrease in the maximum allowable cost of diagnostic screening, and thus to a decrease in its profitability in real medical practice. The introduction of new treatments and the corresponding increase in the utility of PAP detection have the most positive effect on the profitability of the PAP diagnostic screening program. This cost-effectiveness analysis is the first attempt to evaluate the economic value of reducing the delay in PAH diagnosis compared to its benefits to the health care system and society as a whole

Development conceptual of pharmacoeconomic model of technology for early diagnosis and pharmacotherapy of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a poor prognosis in the absence of timely diagnosis and appropriate therapy. Despite significant advances in the treatment of PAH, many patients remain undiagnosed years after the onset of the disease. Evaluation of the implementation of early diagnostic technologies for PAH is increasingly being used to develop economic evidence for health care at the early stages of diagnosis. The development of models of early diagnosis technology for LAH is highly relevant and can be used in the development and management of new medical technologies, as well as to reduce the perceived risks during the implementation of screening programs for LAH diagnosis. The objective of the paper: Conceptual development of a pharmacoeconomic model of the technology of early diagnosis and pharmacotherapy of PAH. Our pharmacoeconomic analysis is based on the «cost–effectiveness» model, which reflects the effectiveness and associated costs of implementing diagnostic screening for early detection of patients with PAH. The analysis of input data of the existing health care system was conducted using systematic review, documentary, informational and graphical research methods. The presented pharmacoeconomic model describes not only the structure of the incidence of PAH in the studied risk group or at the level of the entire population, but also takes into account the pharmacoeconomic evaluation of the complex technology of timely medical care for patients with PAH based on diagnostic screening. A pharmacoeconomic model of the technology of early diagnosis and pharmacotherapy of pulmonary arterial hypertension was developed, which covered a horizon of 10 years and was conducted from the point of view of the existing health care system, showed that for patients with delayed diagnosis of PAH, the modeling determined the average life expectancy at the level of 4.13 years and 2.08 QALYs. It has been determined that a diagnostic screening strategy for PAH would be cost–effective compared to no screening at different thresholds of diagnostic cost. However, other factors such as public awareness and acceptance of the screening programme and availability of human resources should be considered

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

Cellular location and activity of Escherichia coli RecG proteins shed light on the function of its structurally unresolved C-terminus

RecG is a DNA translocase encoded by most species of bacteria. The Escherichia coli protein targets branched DNA substrates and drives the unwinding and rewinding of DNA strands. Its ability to remodel replication forks and to genetically interact with PriA protein have led to the idea that it plays an important role in securing faithful genome duplication. Here we report that RecG co-localises with sites of DNA replication and identify conserved arginine and tryptophan residues near its C-terminus that are needed for this localisation. We establish that the extreme C-terminus, which is not resolved in the crystal structure, is vital for DNA unwinding but not for DNA binding. Substituting an alanine for a highly conserved tyrosine near the very end results in a substantial reduction in the ability to unwind replication fork and Holliday junction structures but has no effect on substrate affinity. Deleting or substituting the terminal alanine causes an even greater reduction in unwinding activity, which is somewhat surprising as this residue is not uniformly present in closely related RecG proteins. More significantly, the extreme C-terminal mutations have little effect on localisation. Mutations that do prevent localisation result in only a slight reduction in the capacity for DNA repair. © 2014 The Author(s)

Using Fluorescence Recovery After Photobleaching (FRAP) to study dynamics of the Structural Maintenance of Chromosome (SMC) complex in vivo

The SMC complex, MukBEF, is important for chromosome organization and segregation in Escherichia coli. Fluorescently tagged MukBEF forms distinct spots (or 'foci') in the cell, where it is thought to carry out most of its chromosome associated activities. This chapter outlines the technique of Fluorescence Recovery After Photobleaching (FRAP) as a method to study the properties of YFP-tagged MukB in fluorescent foci. This method can provide important insight into the dynamics of MukB on DNA and be used to study its biochemical properties in vivo

Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours