bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience in the open multicenter randomized controlled trial of Rheo-STAT on the efficacy and safety of Reosorbilact in patients with sepsis
Authors: Cojocaru V.I. 
Published: July 2021

Background. Elimination of intoxication syndrome is one of the main components of sepsis treatment. The Rheo-STAT study is an interventional open multicenter randomized controlled trial of the efficacy of Reosorbilact (“Yuria-Pharm”) in the treatment of intoxication syndrome. The study was conducted in 7 countries, patients of the sepsis subgroup were recruited in 5 of them (Ukraine, Moldova, Georgia, Kazakhstan, Uzbekistan).
Objective. To determine the efficacy and safety of Reosorbilact in patients with sepsis.
Materials and methods. The study involved 628 adult patients with sepsis, peritonitis, pneumonia and burns. The subgroup of sepsis consisted of 180 people (72 % males, mean age – 41.3 years), the most common comorbidities were cardiovascular diseases (24 %), diabetes mellitus (15 %), and infectious diseases (8 %). The inclusion criteria were the following: age 18-60 years, diagnosis of sepsis, established by the ACCP/SCCM criteria ≤24 hours before the initial visit, obtaining of the informed consent, baseline SOFA scale value ≥2. The primary endpoint was the total score on the SOFA scale on the 3rd day of treatment compared to the baseline value. The secondary endpoints included the change in the overall score according to the APACHE II, SAPS II, MODS, PSI/PORT, CURB-65 scales; changes in biochemical, immunological and integral markers of endogenous intoxication.
Results and discussion. Low-volume infusion therapy with Reosorbilact (200-400 ml per day) resulted in an increase in circulating blood volume and a decrease in the total volume of infusions required without the risk of volume overload, which is especially important for critically ill patients. Exogenous lactate in Reosorbilact did not increase the content of endogenous lactate (1st day – 2.27 mmol/L, 3rd day – 1.63 mmol/L), which indicates the high safety of the solution. In the complex of intensive care administration of Reosorbilact helped to reduce hyperthermia (1st day – 38.2 °C, 3rd day – 36.8 °C, p<0.001), heart rate (1st day – 95.43 beats/min, 3rd day – 81.13 beats/min, p<0.001) and the number of leukocytes (1st day – 14.5×109/L, 3rd day – 8.8×109/L) as a marker of endogenous intoxication. During 3 days of therapy Reosorbilact also normalized the acid-base composition of the blood.
Conclusions. 1. Elimination of intoxication syndrome is one of the main components of sepsis treatment. 2. Reosorbilact infusion therapy increases the volume of circulating blood without the risk of volume overload. 3. The inclusion of Reosorbilact in the complex treatment of sepsis after 3 days provides a decrease in body temperature, heart rate, white blood cell count and normalization of the acid-base composition of the blood.
Diabetic foot: diabetic ulcer care
Authors: Bolgarska S.V. 
Published: July 2021

Background. Diabetic foot syndrome (DFS) is the presence of an infection and/or ulcer defect of the foot associated with neuropathy and circulatory disorders of the lower extremities of varying severity. Insensitivity of the foot, its deformation and constant load lead to the formation of necrosis under hyperkeratosis with the potential infectious process development.
Objective. To describe the features of the course and treatment of DFS.
Materials and methods. Analysis of literature data on this issue.
Results and discussion. Classification of diabetic ulcers is carried out according to the PEDIS system, where P means perfusion, E – extent, D – depth, I – infection, S – sensation. To assess the circulatory status of the lower extremities, the ankle-brachial index (ABI) and transcutaneous oxygen tension are determined. Critical ischemia is determined by the following criteria: tibial systolic blood pressure <50 mm Hg, big toe blood pressure <30 mm Hg, or transcutaneous oxygen tension <30 mm Hg, or ABI <0.5. DFS treatment involves unloading the foot with the help of special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, surgery, antibiotic therapy. If necessary, anti-pseudomonad antibiotics should be used (ceftazidime, cefoperazone, cefepime, imipenem, meropenem, ciprofloxacin, amikacin). 95 % of the microorganisms present in the world are able to coexist in the form of biofilms – communities of microorganisms in a matrix of polymers (mucopolysaccharides), which are released by the same bacteria. Taking this into account, one should choose antibiotics that can penetrate biofilms. Diabetic ulcers should be covered with dressings such as Hydroclean plus, which contain an antiseptic that protects the wound from secondary infection, prevents excessive evaporation of moisture and has an atraumatic contact layer that prevents traumatization of the young granulation tissue. This dressing continuously releases Ringer’s solution into the wound and absorbs the wound exudate, creating a continuous washing effect. Lacerta (“Yuria-Pharm”) can be used to stimulate the regeneration of long-term defects of connective tissues. Lacerta activates the migration and proliferation of fibroblasts, accelerates their metabolic activity, and enhances angiogenesis. Other methods of accelerating of the wound healing include the use of cryopreserved amniotic membranes and the injection of stem cells.
Conclusions. 1. DFS is the presence of an infection and/or ulcerative defect of the foot associated with neuropathy and circulatory disorders of the lower extremities. 2. Classification of diabetic ulcers is carried out according to the PEDIS system. 3. Treatment of DFS involves unloading the foot with special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, antibiotic therapy, surgery. 4. It is advisable to cover diabetic ulcers with hydrogel bandages. 5. Lacerta can be used to stimulate the regeneration of persistent skin defects.
Perioperative anesthesia
Authors: Lisnyi І.І. 
Published: July 2021

Background. Ensuring adequate analgesia is a prerequisite for rapid recovery after surgery. Improving the management of acute pain is important to ensure the safe and effective analgesia needed for early mobilization and for avoidance of organ dysfunction due to inadequate analgesia. For this purpose, multimodal analgesia (MMA) is used. It includes opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAID), paracetamol or metamizole, local anesthetics and ancillary drugs.
Objective. To describe modern views on perioperative analgesia.
Materials and methods. Analysis of literature data on this issue.
Results and discussion. MMA involves an opioid-preserving approach (reducing the dose of opioids without reducing the quality of analgesia), procedure and patient specificity. The postoperative recovery improvement program includes several items, three of which have been associated with a reduction in treatment duration, namely, multimodal prevention of postoperative nausea and vomiting, perioperative NSAID use, and post-operative opioid protocol. The combined use of NSAID and paracetamol provides a better result than the use of each of these drugs alone. At the correct dose, paracetamol (Infulgan, “Yuria-Pharm”) is an effective non-opioid analgesic for the treatment of acute pain with minimal side effects for a long time. Pre- and intraoperative administration of paracetamol is recommended in a number of guidelines. Intravenous administration of local anesthetics is an another important component of MMA. The 2016 Cochrane review showed that long-term intravenous perioperative infusion of lidocaine significantly reduced the postoperative need for opioids. However, the meta-analysis of 10 randomized controlled trials found that perioperative intravenous lidocaine did not differ from placebo in post-operative pain assessed with the help of a visual analog scale and in opioid requirements (Rollins K.E., 2020). Similar results have been obtained in other studies in recent years. Inclusion of nefopam in MMA can reduce the dose of opioids. The use of nefopam, paracetamol and deksketoprofen makes it possible to dramatically reduce the use of morphine. Neither pain nor postoperative recovery can be adequately controlled with a single treatment due to the multifactorial nature of the problem. It is recommended to use MMA, but there are no recommendations for optimal combinations of analgesics for specific procedures. Administration of paracetamol and NSAID in combination with the use of regional techniques is a golden standard of MMA.
Conclusions. 1. After the surgery, the patient should be adequately anesthetized. 2. To achieve optimal, preferably non-opioid, analgesia, it is recommended to use MMA. 3. NSAID, paracetamol, nefopam and regional techniques are the important components of MMA.
Neuroinvasion and neurological complications in COVID-19
Authors: Loskutov O.A. 
Published: July 2021

Background. Coronavirus disease (COVID-19) affects not only the alveoli but also the central nervous system. The pathogenesis of neurological complications of COVID-19 is based on the receptor damage, cytokine-mediated injury, damage of the nervous system due to hypoxia, and neuronal damage due to the retrograde transport of the virus through nerve fibers.
Objective. To determine the mechanisms of coronavirus neuroinvasion and treatment of neurological complications COVID-19.
Materials and methods. Analysis of literature sources and own research on this topic.
Results and discussion. In 3 days after infection viral antigens are detected in the olfactory sensory neurons of the nasal cavity epithelium, which confirms the transnasal invasion of coronaviruses. According to various authors, 36.4-84 % of patients with COVID-19 have neurological manifestations. In general, neurological symptoms of COVID-19 can be divided into three categories: symptoms of the central nervous system disorders (headache, dizziness, consciousness disorders, nausea and vomiting, ataxia, acute cerebrovascular disease, and epilepsy), symptoms of the peripheral nervous system disorders (hypogeusia, hyposmia, hypopsia, and neuralgia) and musculoskeletal symptoms. As viral infections cause cytokine storm, inflammation and hyperactive oxidation, it is advisable to use antioxidants in their treatment. According to the Japanese clinical guidelines for the treatment of acute respiratory distress syndrome, edaravone may be used as a free radical scavenger in such patients. In the experiment, edaravone reduced the area of infarction and promoted functional recovery in cerebral thrombosis. Other properties of edaravone include the prevention of excessive permeability of the pulmonary vessels’ endothelium. Own research has shown that edaravone (Ksavron, “Yuria-Pharm”) reduces the severity of inflammation and mortality in patients with COVID-19. In the control group, the level of the proinflammatory mediator interleukin-6 exceeded the upper limit of normal values by 1652.40 %, and in the Ksavron group – only by 269.97 %. Mortality in the control group was 14.3 %, and in the Ksavron group – 0 %.
Conclusions. 1. Coronaviruses affect not only the lungs but also the nervous system. 2. Neurological symptoms of COVID-19 include headache, dizziness, consciousness disorders, nausea and vomiting, ataxia, acute cerebrovascular disease, hypogeusia, hyposmia, hypopsia, neuralgia, and musculoskeletal symptoms. 3. Edaravone (Ksavron) reduces the severity of inflammation and has an antioxidant effect, which justifies its use in COVID-19.
Presentation of European Society of Oncology Pharmacy: the need in standartization of modern oncology / oncology pharmacy (QUAPOS)
Authors: Meier K. 
Published: July 2021

Background. Ljubljana declaration (2006) states that the close cooperation between oncologists and oncopharmacologists is vitally important to provide an optimal medical care. Multiprofessional approach allows to increase the cost-effectiveness of treatment and to make it safer.
Objective. To prove the importance of the multiprofessional approach and cooperation of various specialists in the oncology field.
Materials and methods. Analysis of the literature data on this topic.
Results and discussion. According to the questionnaires’ results, 59 % of the respondents want to receive information about drugs and their side effects from the pharmacist. It explains the importance of creation of European Society of Oncology Pharmacology (ESOP), which at the moment includes 63 countries. Key principles of ESOP are the compliance to the standards of treatment quality, continuous professional growth and multiprofessional collaboration. Tasks of ESOP include the increase of the compliance to the oral drugs for cancer treatment, the struggle with the lack of drugs in all the world and the providing safety for patients and healthcare workers, which works with cytotoxic drugs (CTD). According to the data of different authors, low adherence can be predicted by the depression and cognitive disorders, side effects of drugs, asymptomatic disease course, difficult and expensive treatment, unsatisfactory control of treatment, etc. Talking about lack of drugs, since 2000s their frequency has increased. Even the drugs, which are included in the List of the Essential Medicines, are not available in every country, that’s why doctors have to change treatment regimens, interchange drugs, decrease the doses and postpone treatment. Struggle to fight the environmental pollution by CTD is one more task of ESOP. Studies have revealed that the most polluted surfaces in hospitals include working surfaces, floors, counters, drug fridge doors. In general, such characteristics as patient-centricity, multidisciplinary and multiprofessional approach, general coordination of treatment process, defined responsibilities, strict treatment protocols, continuous education of medical stuff, and advanced information systems are the most important for high-quality medical care. ESOP also focuses on the increase of pharmacist’s influence, that’s why this organization provides specialized webinars, trainings and workshops in oncology pharmacy field.
Conclusions. 1. High-quality of medical care in cancer needs a pharmacist involvement. 2. Key principles of the ESOP include the compliance to the standards of treatment quality, continuous professional growth and multiprofessional collaboration. 3. Tasks of ESOP include the increase of the compliance to the oral drugs for cancer treatment, the struggle with the lack of drugs in all the world and the providing safety for patients and healthcare workers.
Ketosis in pregnant women: causes, consequences, and correction
Authors: Medved V.I. 
Published: July 2021

Background. Compared to 2013, in 2019 the number of pregnancies in Ukraine decreased by 32.7 %, so the value of each pregnancy and medical liability have proportionally increased. Because pregnancy is a ketogenic and diabetogenic condition, the issue of ketosis in pregnant women requires close medical attention.
Objective. To describe the causes, consequences and correction of ketosis in pregnant women.
Materials and methods. Analysis of literature sources on this issue.
Results and discussion. Ketosis of pregnant women is divided into diabetic and non-diabetic. The total prevalence of ketosis is 1.7-3.6 %. Risk factors for ketosis in pregnant women include starvation, dehydration, decreased blood buffer capacity, increased production of contrainsular hormones and stress. In addition, ketosis is facilitated by the fact that placenta produces placental lactogen (in late pregnancy – up to 1 g per day) – a powerful contrainsular hormone and ketogenic agent (via stimulating lipolysis in the liver). The development of ketosis is usually provoked by infections, acute diseases, and taking certain medications (glucocorticoids, adrenoblockers). In settings of ketoacidosis, the fetus develops bradycardia, hypoxia and distress, ante- and perinatal mortality increases. If the mother has ketosis with β-oxybutyrate in blood and keto acids in the amniotic fluid, it causes behavioral and intellectual disorders in the child. The links of ketosis pathogenesis include energy starvation due to poor nutrition and/or impaired insulin production, lipase activation with the formation of ketone bodies, protein breakdown, hyperglycemia development, and oxidative stress. The majority of cases of ketosis are diagnosed at the stage of decompensation. Polyatomic alcohol xylitol is one of the main means to eliminate ketosis. Xylitol (Xylate, “Yuria-Pharm”) promotes the formation of glycerophosphate in the pentose phosphate cycle, enhances glycogen production, reduces lipolysis, increases ATP level in liver, promotes insulin production, reduces lactate. The inclusion of Xylate (6-8 ml/kg of body weight for 3 days) into the ketosis therapy can significantly accelerate the elimination of ketosis. Xylate does not increase glucose levels and has nitrogen-sparing properties.
Conclusions. 1. Pregnancy is a ketogenic condition. 2. Ketoacidosis of pregnant women is associated with high perinatal losses. 3. Xylate has shown high antiketogenic activity and a number of additional beneficial effects.
Principles and rationale of infusion therapy in tuberculosis
Authors: Petrenko T.I. 
Published: July 2021

Background. In 2018 7 million new cases of tuberculosis (TB) were registered, which is more than in previous years. Undoubtedly, TB is one of the most important threats to the public health globally. In developing countries, where there are no new TB drugs (TBD) and modern medical services, this threat is even more serious. Intravenous administration is an option to optimize the existing drug regimens, as it is accompanied by increased bioavailability.
Objective. To substantiate the rationality of infusion therapy in TB.
Materials and methods. Analysis of literature data on this topic; own study involving 106 patients with newly diagnosed infiltrative and disseminated pulmonary TB with bacterial excretion.
Results and discussion. The medical community is concerned not only about the increase in the TB incidence, but also about the increase in the number of drug resistance (DR) cases. Improper treatment is one of the causes of DR. In case of oral administration absorption disorders of the drug are possible in people with digestive system diseases, in addition, part of the drug is metabolized by passing through the liver. In contrast, intravenous drugs enter the superior vena cava system, right ventricle, and pulmonary arteries. In a number of patients’ subgroups, it is not possible to achieve a sufficient concentration of drugs in serum when taken orally for various reasons. In particular, these reasons include host organism factors (features of drug metabolism (fast acetylators are more likely to have DR than slow ones), malabsorption, drug clearance, inability of the drug to reach lung tissue) and mycobacteria factors (biofilm formation, drug resistance due to efflux pumps, metabolic status of the bacterium – division phase or sleep phase). These factors are considered to be the consequences of continuous oral administration of TBD. Achieving a high concentration of TBD in the source of infection due to intravenous administration allows to overcome the DR of mycobacteria. In the own study, oral (n=33) and intravenous (n=73) modes of TBD administration were compared. The groups were identical in age, sex, and TB stage. In the intravenous treatment group there was a significantly higher proportion of complete closure of the decay cavities (90.5 % vs. 60.4 % in the oral treatment group; p=0.04), as well as the significantly lower number of toxic reactions (14.3 % vs. 57.9 %; p=0.001) and poor tolerability of treatment (31 % vs. 57.9 %; p=0.04). On the background of intravenous therapy less fluoroquinolone DR was observed.
Conclusions. 1. Intravenous therapy in patients with pulmonary TB is more effective than standard in terms of closure of the decay cavities. 2. Intravenous therapy is accompanied by significantly less toxicity and better tolerability. 3. Intravenous TB therapy is less likely to provoke the development of DR.
Malabsorption syndromes in patients with tuberculosis as a cause of ineffective treatment: how to diagnose and overcome?
Authors: Butov D.O. 
Published: July 2021

Background. Impaired drug absorption is one of the reasons of the ineffectiveness of tuberculosis (TB) treatment. Malabsorption syndrome (MS) is a clinical syndrome that occurs due to the impaired digestive and transport function of the small intestine and is characterized by impaired absorption of nutrients, vitamins, microelements and drugs from the digestive tract. MS accompanies the following pathological conditions: pancreatic diseases, cholestasis, inflammatory bowel diseases, autoimmune enteropathies, diabetes mellitus, amyloidosis, hyperthyroidism, atrophic gastritis, HIV/AIDS, infections and parasitosis of the digestive system, alcoholism, and TB.
Objective. To describe the ways to overcome the influence of MS on TB treatment.
Materials and methods. Analysis of literature data on this topic.
Results and discussion. MS can worsen the treatment of all forms of TB, especially severe. The latter include tuberculous meningitis, disseminated TB, miliary TB, caseous pneumonia, and infiltrative TB. Causes of death from severe forms of TB include untimely diagnosis, lack of thorough differential diagnosis, insufficient intensity of therapy, decreased maximum concentration of oral forms of anti-TB drugs (ATBD) in blood. The latter often occurs in severe forms of TB and in case of co-infection with TB and HIV/AIDS. Injectable forms of the drugs are recommended by the World Health Organization to increase the effectiveness of TB meningitis treatment. The American Thoracic Society and the American Society of Infectious Diseases also recommend the use of intravenous ATBD in patients with impaired absorption. Most patients receiving oral ATBD have extremely low plasma concentrations of these drugs. This is probably due to a decrease in the functional area of intestinal absorption in patients with TB. Indications for intravenous ATBD include severe forms of TB, the presence of severe disorders of the digestive system and severe comorbidities, TB with multiple and widespread resistance to ATBD, pre- and postoperative periods, low adherence to therapy. The intensive phase of therapy and the patient’s preference may be the additional indications. Studies show that intravenous ATBD is associated with significantly better survival than oral, in the absence of an increase in the number of side effects. The advantages of intravenous administration also include 100 % bioavailability, 100 % controllability of treatment, intensification of therapy, overcoming and preventing the development of resistance of mycobacteria, reducing the risk of adverse reactions, improving the tolerability of chemotherapy.
Conclusions. 1. Impaired drug absorption is one of the reasons for the ineffectiveness of TB treatment. 2. MS can worsen the treatment of all forms of TB, especially severe. 3. In patients with malabsorption it is recommended to use intravenous ATBD. 4. Intravenous ATBD is associated with significantly better survival than oral, in the absence of an increase in the number of side effects.