Modern achievements in pharmacotherapy of osteoarthritis based on endo- and phenotyping

The review of medical literature is devoted to modern data in the field of diagnosis and treatment of osteoarthritis using endo- and phenotyping. It includes the latest data on the epidemiology of osteoarthritis of different localizations, modern definitions and classifications of osteoarthritis endotypes and phenotypes, pathobiochemical patterns and pathomorphological parallels of disease phenotypes, new methodological approaches to the phenotyping of osteoarthritis (prognostic, prescriptive phenotyping, alternative methods), as well as modern advances in pharmacotherapy of the disease based on data from selected randomized controlled trials and meta-analyzes.

The concept of syndromic diagnoses of osteoarthritis and back pain as a cause of therapy failure

Osteoarthritis is considered a peripheral joint disease and is often ignored when discussing the prevalence and treatment of back pain. Traditionally, clinical guidelines from various countries are devoted to the treatment of nonspecific back pain (lower back pain), although this diagnosis is syndromic and is absent in ICD-10. Therefore, in real clinical practice, such diagnoses as osteochondrosis and dorsopathy simultaneously exist. The treatment strategies for back pain do not take into account chronic inflammation directly related to pro-inflammatory cytokines and oxidative stress, which makes drug therapy ineffective. It is advisable from the first days of therapy to choose parenteral forms from the group of symptomatic slow-acting drugs containing chondroitin sulfate (Chondroguard®), which will accelerate the onset of the analgesic effect and increase the effectiveness of pathogenetic therapy.

Pharmacoeconomic evaluation of the effectiveness of therapy for metastatic colorectal cancer

Objective: to perform a pharmacoeconomic evaluation of the effectiveness of therapies for metastatic colorectal cancer (mCRC) based on real practical data on medical help for patients with this disease.Material and methods. The authors performed a comparative cost-effectiveness analysis and the calculation of resource consumption in the application of several options of chemotherapy for mCRC: FOLFOX, FOLFIRI, and FOLFOXIRI; targeted therapy: FOLFOX + bevacizumab, FOLFOX + panitumumab, FOLFIRI + cetuximab, FOLFIRI + aflibercept, regorafenib monotherapy.Results. The cost-effectiveness parameter, calculated as a ratio of the cost of therapy to the median survival without progression, for chemotherapeutic schemes varied from 108 to 167 thousand rubles and for the targeted therapy schemes – from 223 to 930 thousand rubles. The calculation of resource consumption showed that in the case of a limited budget, 100% of patients can be treated by FOLFOX scheme, or 26% of patients by FOLFOX + panitumumab, or 47% of patients by FOLFOX + bevacizumab; and 100% of patients by FOLFIRI scheme or 11.5% of patients by FOLFIRI + cetuximab (aflibercept). Besides, it was established that in the case of a similar budget, 100% of patients with mCRC can be treated by chemotherapy schemes or a limited number of patients with regorafenib.Conclusion. The cost of targeted therapy significantly exceeds the cost of chemotherapeutic schemes. Still, considering the gross domestic product per capita in the Russian Federation, they can be an economically feasible investment and the optimum option of therapy

An economic evaluation of pre-dialysis stage of chronic kidney disease

Objective: to review clinical and economic studies on the pre-dialysis stage of chronic kidney disease (CKD) and the cost-effectiveness of medical interventions used to detect CKD and prevent its progression.Material and methods. Articles were collected from the bibliographic databases PubMed, Cochrane Library and eLibrary for 2010–2020. Keywords for the search: ‘chronic kidney disease (CKD)’, ‘cost-effectiveness’, ‘economic evaluation’, ‘economic burden’, ‘cost’, ‘healthcare’. After the selection and elimination of the repeated articles, we reviewed 36 Russian and foreign studies on the economic burden of CKD and the clinical and economic effectiveness of various medical interventions of the CKD pre-dialysis stage.Results. We found 21 studies on the economic burden of CKD. A significant part of them (n=6) was performed in the United States.The methodology for assessing the economic burden varied significantly from study to study. Studies on medical interventions at the CKD predialysis stage can be divided into three groups: Group 1 (n=9) – studies on the clinical and economic effectiveness of screening programs; Group 2 (n=3) – studies on the clinical and economic effectiveness of nephroprotectors and other drugs that slow down the course of CKD; and Group 3 (n=3) – studies on the clinical and economic effectiveness of multidisciplinary care. We concluded on the clinical and economic feasibility of most interventions that were used to detect CKD and prevent its progression.Conclusion. We did not find any scientific data that could currently serve as a justification for the clinical and economic feasibility of CKD control programs in the Russian Federation. At the same time, studies conducted in foreign countries on the screening for CKD and some interventions aimed at slowing the progression of CKD suggest that in the Russian Federation, such approaches can be justified not only clinically, but also economically. It is necessary to conduct domestic research on the clinical and economic feasibility of interventions aimed at identifying and treating CKD at an early stage.

Review of methods for planning the scope of medical care and financing of the healthcare system by the subjects of the Russian Federation

The article presents a review of current and alternative methods for planning the scope and financing of medical care in the subjects of the Russian Federation. The relevance of the issue is due to the imperfection of the current planning model, which stimulate representatives of the profile bodies and independent experts to develop alternative methods. The current approaches and legal documents regulating the procedure for distributing the scope of medical care and financial resources to pay for this care are discribed. The analysis of alternative methods shows how different demographic and infrastructural features of regions can be used to redistribute the scope of medical care and the corresponding financial support.

Peculiarities of administration of medications to patients with circulatory system diseases within the framework of the federal program of preferential provision of medicines

Objective: to analyse of medicines prescriptions for federal beneficiaries with circulatory system diseases and to identify the main trends in the implementation of the federal program for the provision of necessary medicines in the Samara Region in 2014–2017.Material and methods. The authors reviewed the nomenclature of medicines used to treat circulatory system diseases (CSDs) and distributed to the population of the Samara Region as part of the federal program for the provision of necessary medicines for the period from 2014 to 2017. The methods of comparative, retrospective, logical, graphical and content analysis, the method of data grouping according to Anatomical Therapeutic Chemical classification and methods of descriptive statistics were used.Results. In 2014–2017 the share of financial costs for the purchase of medicines in the total budget of the federal program for the provision of necessary medicines in the Samara Region did not exceed 6%. Still, in physical terms (in terms of the number of packages) the share of medicines of this pharmacotherapeutic group in the federal program for the provision of necessary medicines averaged about 25%. Nomenclature of medicines of the analyzed group prescribed to federal beneficiaries in 2014–2017 ranged from 90 to 107 nomenclature items. The number of international nonproprietary names (INN) decreased from 51 in 2014 to 36 in 2017. During the period under review, there was a decrease in the acquisition cost of medicines for the treatment of circulatory system diseases and the weighted average cost of one package (by 63% and 53%, respectively).Conclusion. Perindopril-containing medicines occupied the maximum consumption volumes in monetary terms. There was a decrease in the average cost of one package in 2017, which may be associated with the replacement of original medicines with generics and a concomitant reduction in the number of INN within the subgroup.

History of controlled trials in medicine: real priorities are little-known. Report 2. From early experiments to the present day: without alternation and randomization

The aim of the three-report review is the historical development of clinical trials, controlled trials (CT) and randomized controlled trials (RCT), and the inclusion of these approaches in health-related disciplines (Medicine and Epidemiology). Report 2 provides a description of the wellknown James Lind Library (JLL), as well as a formed database of sources on the theme. JLL was internationalized, although most of the papers belong to authors from the UK. Many studies on the history of CT and RCT are reflected in JLL publications, but remain unclaimed without changing on common milestones and priorities. Besides, the formed base of sources included 9 studies not reflected in the JLL, of which three are principled. Six of them are given in Report 2.Half of historical milestones on the theme (168 in total) belong to the United Kingdom, 23% to the United States, and 4% to the Italy. The remaining 19 countries, ancient, medieval and modern, contribute 0.6–4% (Russia – 1.2% by the 20th century). The earliest source on the history of CT is J.P. Bull’s dissertation (1951). The formed database as of July 2020 contained more than 260 publications, and only 9 of them were Russian (2005–2018). The base includes 7 western dissertations on the history of CT.The object of the Report 2 study was CT as such, without any attempts at randomization or even quasi-randomization by alternate allocation. The most comprehensive thematic table on non-randomized CTs has been compiled, including studies from the Chinese emperor Shen Nung (2373 BC) and the prophet Daniel (6th century BC), to BCG vaccination for children of Canadian Indians (1941–1949). PubMed search on ‘non-randomized controlled trial’ was made. For the period of 1990–2020 years, 303 publications were found (up to 32 papers in 2020). Compared to RCT, the number of such studies is small (estimated at 0.08%), but it is important to have an appropriate conjuncture in the modern period. Along with the fact that most of the drugs and therapies currently in use are developed without RCT, the revealed ‘immortality’ of CT, even without quasi-randomization, can have social significance, removing complexes and embarrassment in cases where neither RCT nor even quasi-RCT is possible, but social and public needs require the immediate receipt of at least an approximate answer to hot questions of public health (for example, in 2020).

Pharmacoeconomic analysis of the application of strong opioids for the treatment of chronic pain syndrome in patients with pancreatic cancer

Objective: to evaluate the clinical and economic feasibility of opioid therapy based on the analysis of its cost and effectiveness in patients with chronic pain syndrome in pancreatic cancer.Material and methods. An observational prospective study in parallel groups of patients with chronic pain syndrome associated with pancreatic cancer was carried out. The analysis of cost minimization and cost-effectiveness was applied, as well as pharmacoeconomic modeling, which included the construction of a decision tree in patients receiving morphine sulfate (n=45) and fentanyl TTS (n=45) for pain relief. The sensitivity of the obtained data was assessed using one-way analysis.Results. It was shown that the treatment of chronic pain syndrome in patients with pancreatic cancer with opioid analgesics as part of combined treatment is the least expensive in the morphine sulfate group (incremental cost-effectiveness ratio 144.93). Based on the results of modeling, the prognostic factors of influence on the cost of analgesic therapy were determined: the cost of combined analgesic therapy, the cost of treatment of adverse reactions, and the cost-effectiveness ratio.Conclusion. Analgesic therapy of chronic pain syndrome with morphine sulfate in patients with pancreatic cancer is pharmacoeconomically feasible.

Increasing the medico-economic efficiency of preventive counseling for patients with arterial hypertension and behavioral risk factors for non-communicable diseases

Objective: to evaluate behavioral risk factors (BRF) in patients with arterial hypertension (AH) and to determine the ways of improvement of the approaches to preventive consulting targeted to increase medico-economic efficiency of the prevention of cardiovascular diseases (CVDs).Material and methods. A total of 107 patients aged 40–60 years old that attended health-promoting schools for patients with AH at the institutions of primary medical help in Moscow in 2017–2019 were surveyed. The authors used diagnostic criteria of the risk factors for noncommunicable diseases that have behavioral character according to the classification of the World Health Organization (WHO). Along with that, the authors reviewed the opinion of 128 top managers of the institutions of primary medical help that attended the courses of their qualification improvement “Organization of public healthcare” in 2019. The course was dedicated to the possible ways of improvement of preventive consulting of patients with AH and BRF. The methods of content analysis, synthesis, statistical analysis, comparison, etc. were applied. The authors analyzed the documentation on the prevention of CVDs, scientific publications on the subject from eLibrary, Cochrane Library, PubMed, Scopus databases, and official sites of biomedical journals.Results. The sociological survey revealed data on the presence of BRF of non-communicable diseases in patients aged 40–60 years old with verified AH based on scientifically proven criteria and WHO classification. These criteria allowed to evaluate the degree of the proneness of patients with AH to the influence of harmful risk factors (smoking, alcohol consumption, lack of physical activity, unhealthy eating habits) and their combinations. The sociological survey data obtained from the top management of institutions of primary medical help indicated the necessity of the improvement of approaches to group preventive consulting of patients with AH and BRF.Conclusion. The results of the study revealed the main areas of the systemic mistakes in the preventive consulting of patients with AH that have BRF, associated with the evaluation of individual-psychological peculiarities of a personality, and in the organizational aspects of preventive counseling.