Risks of using pre-event time scale and ordinal scale measurements in COVID-19 clinical trials

BACKGROUND. The article shows the results of literature search and analysis of endpoints of interventional clinical trials of phase III-IV of the treatment of hospitalized patients with coronavirus disease (COVID-19) and of its prevention. MATERIALS AND METHODS. Among 102 trials found, ordinal scales were used in 60 trials, time-to-event outcome measures were used in 54 trials, both scales – in 49 trials. Time-to-event endpoints were related to hospitalization/intensive care unit term, discontinuation of oxygen therapy, and clinical improvement standardized on ordinal scales. At the same time, the early discontinuation of oxygen therapy and the early discharge create risks to the biometric measurement. RESULTS AND DISCUSSION. Statistical calculations showed the association of the number of new COVID-19 hospital admissions per day with the percentage of free beds, but not only with the number of new coronavirus infection cases in general, the number of deaths and the number of people recovering from COVID-19 per day in different regions of Ukraine. These results may indicate that resource-dependence and organizational aspects affect the hospitalization of patients with COVID-19. CONCLUSIONS. Therefore, to ensure that the discharge or discontinuation of oxygen therapy was due solely to a positive clinical outcome, data on changes of number of beds, access to oxygen supplies as well as data relevant to determination of the desired clinical outcome (body temperature, oxygen saturation, severity of symptoms, etc.) should be collected. It is recommended to collect biomarker data after discharge, if possible.

Inhaled antiseptics and inhaled antiviral non-prescription drugs in the prevention of ARVI, in particular COVID-19: an epidemiological study

BACKGROUND. The article presents the results of a continuous, cross-sectional, non-interventional, multicenter retrospective epidemiological study, which included cases of 3443 participants. Questionnaires and rapid test for antibodies to SARS-CoV-2 were used to collect data. OBJECTIVE. To determine the relationship between the systematic use of additional drugs for the prevention of COVID-19, including inhaled antiseptics and inhaled antiviral drugs, separately and in combination with other drugs, and the risk of developing of coronavirus disease (COVID-19). RESULTS AND DISCUSSION. 396 participants (11.8 %) took inhaled antiseptics in any period since March 2020, and 410 participants (12.2 %) took inhaled antivirals. A statistically significant protective relationship between episode of COVID-19 when taking inhaled antiseptics and inhaled antiviral drugs (risk ratio 0.901; 95 % confidence interval 0.856-0.948) was determined. CONCLUSIONS. The use of inhaled antiseptics and inhaled antiviral drugs as additional methods of prevention of COVID-19 has shown a statistically significant effect not only on reducing the risk of COVID-19, but different combinations of inhaled antiseptics or inhaled antiviral drugs with other drug groups as additional methods of preventing COVID-19 had a statistically significant protective relationship with the episode of the disease, with the severity of COVID-19 and with the need for hospitalization.

Diagnostics of lesions of parenchymatic organs in COVID-19 with the application of digital software processing of computer tomography images

BACKGROUND. In the third wave of the pandemic, the coronavirus disease 2019 (COVID-19) was more aggressive. The available information on the pathogenesis of respiratory failure was supplemented with new data. Up-date information about the respiratory failure pathogenesis was acquired. It has been shown that the SARS-CoV-2 virus leads to disappearance of white pulp cells in the spleen. In this tissue immune cells mature and differentiate, among others T- and B-lymphocytes, which are responsible for premunition. The study of the structure and function of the spleen has become even more urgent. Some authors note a change in the size of the spleen during ultrasonography and chest computed tomography (CT), which correlate with indicators of the pneumonia“s severity. The study of the structure and function of the spleen has become even more urgent. OBJECTIVE. To study is to evaluate changes in the structure of solid organs (lungs, liver and spleen) in patients with a complicated community-acquired viral pneumonia COVID-19 by means of software digital processing of CT scan data and their comparison with pathomorphological changes. MATERIALS AND METHODS. The analysis of CT data in patients with a complicated community-acquired viral pneumonia COVID-19, who were treated at the SI “National institute of phthisiology and pulmonology named. F.G. Yanovsky of the NAMS of Ukraine”. CT WGC was performed on an Aquilion TSX-101A «Tochiba» scanner (Japan), followed by digital software processing of CT images using the Dragonfly software. Histological preparations were obtained as a result of traditional alcoholic histological tracing of tissue samples, embedded in paraffin blocks. To obtain micrographs, an Olympus BX51 microscope was used with an Olympus DP73 digital camera and a CellSens computer program for image processing. RESULTS AND DISCUSSION. The obtained results of digital software processing of CT images clearly correlate with autopsy histological examination of tissues of the same solid organs. Changes in the structure of the spleen occur earlier than in other solid organs, which gives reason to use these changes for diagnostic purposes. Digital processing of CT images of the spleen allows determining the severity of the disease, predicting its further course and evaluating the effectiveness of treatment. CONCLUSIONS. In patients with a complicated viral (COVID-19) community-acquired pneumonia changes (which can be determined by digital software processing of CT data) in the structure of solid organs, especially in lungs and spleen, were observed and they correlate with pathomorphological changes.

Laboratory evaluation of the efficacy of Liastene application in complex therapy of multiresistant pulmonary tuberculosis

OBJECTIVE. Evaluating according to laboratory tests the effectiveness of Liasten in the treatment of patients with multidrug-resistant pulmonary tuberculosis (MDR-TB). MATERIALS AND METHODS. Evaluation of the effectiveness of etiotropic and etiopathogenetic therapy in 57 patients with MDR-TB was performed. According to the treatment schemes, patients were divided into groups. The control group (n=22) received individualized antimycobacterial therapy (AMBT) regimens. The experimental group (n=35) received AMBT in combination with Liasten. Evaluation of the effectiveness of treatment regimens was performed on the basis of indicators of general clinical blood tests, immunological and bacteriological studies. RESULTS AND DISCUSSION. In patients of the experimental group, compared with the control in 1.5 times more often found positive changes in the hemogram of blood and ESR (p<0.05-0.001), the establishment of a dynamic balance between the pools of lymphocyte cells CD4+ and СD8+ (immunoregulatory index, p<0.05), an increase in the number of phagocytosis active cells (phagocytic index, p<0.05), the content of cationic lysosomal proteins of granulocyte leukocytes (p<0.05), a 1.4-fold decrease in the cytochemical coefficient of neutrophils (p<0.05), the number of proliferated under the action of PPD-L lymphocytes (p<0.05), normalization of phagocytic counts and total redox activity of neutrophils (p<0.05), increase in frequency and reduction of anesthesia was stated. CONCLUSIONS. Restoration of the body’s immune status, blood hemogram, increase in frequency and reduction of the time of decontamination were more active and occurred 1.5 times more often in patients receiving a complex combination of AMBT with Liasten.

The role of vitamin D deficiency in antituberculous protection

BACKGROUND. The main task of modern phthysiology is a comprehensive search for ways to optimize the etiotropic and the pathogenetic treatment of tuberculosis (TB). The search for improved treatment in addition to etiotropic antimicrobial therapy lies in the plane of improving pathogenetic therapy. Analysis of the available scientific sources suggests that the efficacy of TB treatment can be improved by adding vitamin D to the pathogenetic treatment, as vitamin D metabolites support the innate immune response to Mycobacterium tuberculosis. OBJECTIVE. To determine the role of vitamin D in the immunopathogenesis of the inflammatory response in pulmonary TB and to assess the prospects of its impact on improving the effectiveness of treatment by analyzing information from available scientific sources on this topic. MATERIALS AND METHODS. The study was performed for the period December 2020 – August 2021. The search was conducted by Keywords: pulmonary tuberculosis, vitamin D, mechanism of action, pathogenesis, treatment. Access to various full-text and abstract databases was used as the main source of research. RESULTS AND DISCUSSION. A large number of studies conducted so far prove the link between vitamin D deficiency and the occurrence of pulmonary TB. Vitamin D receptors have been found to be present on various surfaces of immune cells, including T and B cells, indicating that they need vitamin D to perform cellular functions. Vitamin D has been shown to increase the phagocytic activity of macrophages, and that monocytes incubated with cholecalciferol (vitamin D3) metabolites induce anti-TB activity. A number of studies have shown that vitamin D increases the body’s production of the antimicrobial/antimycobacterial peptide LL-37, a member of the cathelicidin petelide family. Therefore, the narrowly analyzed analysis according to the literature suggests that in the conditions of full vitamin D status of the human body the course of TB will be favorable, and in case of vitamin D deficiency – which is primarily associated with genetic polymorphisms, the course of TB may be unfavorable. CONCLUSIONS. Vitamin D functionates as one of the activators of macrophages and plays a role in the immune defense of the human body against mycobacterial TB. The inclusion of vitamin D in the program of complex treatment of TB infection is promising, as it enhances the production of antimicrobial/antimycobacterial peptide LL-37. It can be used as one of the components of TB prevention in children.

The impact of the COVID-19 pandemic on the financial sector in medicine: features of centralized state procurement of drugs and medical devices in Ukraine for the period 2018-2021

ABSTRACT. Coronavirus disease (COVID-19) has deeply impacted the global health care system, and the redistribution of funding for medical care violated the prevention and treatment of chronic non-communicable diseases, including hypertension, tuberculosis, and HIV. In 2020, centralized state procurement of medicines in Ukraine was for the first time conducted via the online platform Prozorro. Of the 483 items planned to be purchased, 375 items (78 %) were successfully contracted. In the current 2021, tenders were announced for the purchase of 555 of 562 items. In most fields of medicine, the drugs to be purchased are 100 % covered by tenders. The lowest percentage of coverage is observed for pulmonary arterial hypertension (66.67 %). In today’s complex environment, not only COVID-19 should be actively combated, but other diseases should be also kept in mind when carefully planning the funding of various fields of medicine through the analysis of data from previous years. The money saved can be used to eliminate the consequences of the COVID-19 pandemic, and to purchase the necessary medicines. The creation of a single database of drug residues in medical institutions (chatbot in the Telegram messenger) can be called a positive innovation. Control of drug residues and their adequate redistribution makes it possible to rationally use this resource without spending money on unnecessary purchases. In general, despite the medical and financial impact of COVID-19, Ukraine’s healthcare system continues to withstand pressure and change for the better. Further improvement of the system of centralized procurement of medicines will be able to overcome the problem of lack of necessary drugs.

The problem of hypersensitivity to vitamin preparations

ABSTRACT. The problem of the development of adverse reactions as a result of the use of diagnostic and medicinal products (drugs) is becoming increasingly important. Patients more often report reactions to local anesthetics (43.2 % of cases), antibiotics (18.8 %), nonsteroidal anti-inflammatory drugs (9.7 %), other drugs (28.4 %), B vitamins (4-5 %). It is important to understand that hypersensitivity (HS) to vitamin preparations (VP) is very common, according to patients, but not so often confirmed by their in-depth allergy examination. Basic data on HS before the VP were obtained in the 80-90s of the 20th century, but since then the situation has changed radically. The frequency of HS on these drugs is based on medical history when patients use multicomponent VP for oral administration, allergens in which may be other components (shell tablets and capsules, metal salts, flavors, sweeteners, dyes, preservatives). The causative allergens in the injectable forms of VP can also be auxiliary ingredients of the drug, in particular lidocaine and benzyl alcohol. There are only a few scientific publications with the appropriate evidence base for HS to individual VP, more often B vitamins. The clinical picture of HS reactions to VP is diverse (systemic, cutaneous, respiratory, rarely other visceral manifestations). They can develop both immediately and in a delayed type. Part of the VP (B vitamins, vitamin K) can cause the development of anaphylaxis with fatal consequences. VP, as a rule, do not belong to vital drugs therefore it is possible for this reason till now in real clinical practice insufficiently developed methods of allergodiagnostics both in vivo (skin, provocative tests), and in vitro (laboratory tests) among patients with suspicion for the development of HS to VP. It is not possible to perform allergy diagnostics in persons who have taken complex VP, so there is a problem of hyperdiagnosis of drug allergy to them. Therefore, the problem of determining the true allergic reaction in patients who report the development of a history of HS to VP remains relevant. As a rule, after the development of any adverse reaction during the reception of VP on the patient hangs the label “allergy to vitamins” for life without further allergy examination. That is why the problem of HS to VP needs further study.

Diagnosis of disappearing lung syndrome as a complication of non-hospital pneumonia of viral etiology (COVID-19)

BACKGROUND. Particularly dangerous coronavirus disease (COVID-19) continues to be one of the urgent problems of mankind. Researchers around the world have noted that in the third wave of the COVID-19 pandemic, the disease became more aggressive. Physicians more often began to pay attention to the occurrence of progressive lung degradation, in particular bullous-emphysematous changes in the lungs, and in those patients who did not have a history of chronic lung disease. Due to the fact that in the acute phase of coronavirus infectious computed tomography (CT) of the chest according to the national protocol is not required, the timing of this complication remains unknown. OBJECTIVE. To study the timing of the onset of disappearing lung syndrome as one of the complications of communityacquired pneumonia of viral etiology (COVID-19) and to demonstrate on clinical observations according to CT. MATERIALS AND METHODS. A group of patients referred for treatment to the SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky of the NAMS of Ukraine”. Among the examined according to CT of the chest identified 21 patients (15 men and 6 women aged 24 to 67 years) with radiological signs of disappearing lung syndrome. Nine of them (7 men and 2 women aged 24 to 54 years) were treated at the institute during the acute period of the disease. Another 12 (8 men and 4 women aged 27 to 67 years) were referred to the institute from other medical institutions, where they were treated for community-acquired pneumonia of viral etiology (COVID-19) 3-4 months ago. RESULTS AND DISCUSSION. CT analysis of the chest in 21 patients with disappearing lung syndrome showed that 9 (42,9 %) of them were diagnosed with bullous-emphysematous changes in the acute period of the disease – from 1 to 2 months, and in 12 (57,1 %) – in the postpartum period, in the period from 3 to 4 months. At the same time, patients had difficulty breathing, coughing, no significant improvement in general condition after previous inpatient treatment. Three of 12 patients noted deterioration of the general condition. CONCLUSIONS. In severe patients with community-acquired pneumonia of viral etiology (COVID-19), a progressive pulmonary degradation syndrome with the formation of bullous-emphysematous changes can occur both in the acute period of the disease and develop or progress in the postpartum period (after 3-4 months after inpatient treatment). CT of the chest should be performed in all patients after inpatient treatment and elimination of acute respiratory distress syndrome, which will allow timely diagnosis of changes in lung architecture and complications of the disease.

Forecasting thrombotic complications in patients with community acquired pneumonia according to multidimensional analysis of severity, systematic inflammation, endothelial function and hemostasis

BACKGROUND. Despite the significant progress in the diagnostic and treatment of community-acquired pneumonia (CAP), the issues of timely defining thrombotic complications of CAP and their timely treatment have not yet been fully resolved. OBJECTIVE. To determine the prognostic signs of the risk of thrombotic complications in patients with CAP. MATERIALS AND METHODS. Thus, 45 patients with CAP of the 3rd and 4th clinical groups were examined. The result of the cluster analysis was the distribution of patients into certain clusters (classes). There were 3 clusters of patients depending on the predisposition to thrombosis. RESULTS AND DISCUSSION. Patients belonging to cluster 2 and cluster 3 had a high risk of thrombosis. A feature of these patients was a severe course of CAP (by SMRT-CO scale), accompanied by significant leukocytosis or leukopenia in combination with severe systemic inflammation (C-reactive protein) and low protein C. CONCLUSIONS. This category of patients should consider the possibility of prescribing anticoagulant therapy. While in patients with mild CAP, less pronounced systemic inflammation and high levels of protein C, the risk of thrombosis will be low. Therefore, this category of patients will not require the appointment of anticoagulants.

Dynamics of the incidence of the relapses in patients with pulmonary tuberculosis

BACKGROUND. Among countries of Europe in Ukraine the incidence and mortality rate from tuberculosis (TB), including the incidence of the relapses in patients with pulmonary tuberculosis (RPT), remain high. Absence of the national program of fight from TB, lack of financing of anti-TB measures, unsatisfactory statistical information confirm the necessity of study of situation from relapses in patients with RPT and development of measures on their warning. OBJECTIVE. To estimate the features of dynamics of the incidence of RPT in the last few years and consisting of epidemic situation of TB in a country. MATERIALS AND METHODS. An analysis of official statistical reports of anti-TB establishments of administrative territories of Ukraine, information of SI “Center of Public Health of the Ministry of Health of Ukraine” and SI “Center of Medical Statistics of the Ministry of Health of Ukraine” in the last few years. RESULTS AND DISCUSSION. By the features of dynamics of the incidence of RPT in the last few years in a country are high the incidence in patients with RPT with sputum positive smears with comparison in the incidence in patients with RPT with sputum negative smears; decline of index on 46,0 %; high part of RPT with sputum positive smears among patients with TB sputum positive smears (the TB new cases + relapses); diminishing of amount of cases of TB which the diagnosis of multidrug-resistant TB is confirmed, from them growth of percent of patients with extended resistant of Mycobacterium tuberculosis. The signs of epidemic situation are: decline of the TB incidence of lights (the new cases + relapses); high percent of patients sputum positive smears; high TB incidence among children by age 15-17; diminishing of the TB mortality rate and his prevalence; absence of changes of index prevalence of TB among children by age 0-17 and 0-14. CONCLUSIONS. The analysis of statistical data testifies to the presence of failings in an exposure and treatment of patients with the relapses of TB, on the necessity of introduction of complex anti-TB measures for warning of relapses within the framework of the national program of fight from TB.