Comparison of several alternative uses of targeted antirheumatic drugs in monotherapy for early rheumatoid arthritis

Objective: to evaluate the efficacy of tocilizumab (TCZ) versus tofacitinib (TOFA) in patients with severe and moderate rheumatoid arthritis (RA) who have not previously received methotrexate (MTX). Material and methods. A systematic search for studies dealing with the evaluation of the efficacy of TCZ and TOFA was made in accordance with the provisions of the instruction «Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)». Indirect comparison of two Function and ORAL Start randomized clinical trials was done, as described by Н.C. Buchera. The trials were comparable in their design and in the baseline characteristics of patients. The efficiency of pharmacotherapy for early RA was evaluated based on the ACR20/50/70 response rates in MTX-naive patients from three endpoints. Results. The indirect comparison of TOFA and TCZ (A MTX general control) after 52 weeks of treatment in MT-naive patients with severe and moderate RA indicated that the use of TOFA 5 mg twice daily and TCZ 8 mg/kg showed no difference in ACR20, ACR50, and ACR70 response rates. Nevertheless, there was a tendency to the greater efficiency of TOFA (5 mg twice daily) than that of TCZ (8 mg/kg). The indirect comparison of TOFA (10 mg twice daily) and TCZ (8 mg/kg) established that TCZ therapy was associated with the lower response rate for ACR50 (by 37%): the relative risk (RR) was 0.63; 95% confidence interval (CI), 0.44–0.90 and for ACR70 (by 51%): RR, 0.49; 95% CI, 0.29–0.83 as compared with TOFA therapy. Conclusion. The indirect comparisons confirmed that monotherapy with TOFA (10 mg twice daily) produced a more pronounced antiinflammatory effect than that with TCZ in MTX-naive patients with early severe and moderate RA of less than one year's duration. There were no statistically significant differences in ACR response rates between the TOFA (5 mg twice daily) and TCZ (8 mg/kg) groups

Changes in Prescribing Antithrombotic Therapy in Patients with Atrial Fibrillation in the Multidisciplinary Hospital in Volgograd from 2012 to 2020

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) in real clinical practice, to evaluate changes of prescriptions from 2012 till 2020.Material and methods. The medical records of inpatients (Form 003/y) with the diagnosis AF, hospitalized in the cardiological department were analyzed. According to the inclusion criteria, the patients were over 18 years of age, established diagnosis of non-valvular AF. There were two exclusion criteria: congenital and acquired valvular heart disease and prosthetic heart valves. In retrospective analysis we have included 263 case histories in 2012, 502 ones in 2016 and 524 in 2020. CHA2DS2-VASc score was used for individual stroke risk assessment in AF. The rational use of the antithrombotic therapy was evaluated according with current clinical practice guidelines at analyzing moment.Results. During period of observation the frequency of antiplatelet therapy significantly decreased from 25,5% to 5,5% (р<0.001), decreased the frequency of administration of warfarin from 71,9% to 18,3% (р<0.001). The frequency of use of direct oral anticoagulants increased in 2020 compared to 2016 (р<0.001). For patients with a high risk of stroke anticoagulant therapy was administered in 71.8% of cases in 2012, 88.5% in 2016 and 92.5% in 2020. Before discharge from hospital majority of patients (72%) achieved a desired minimum international normalized ratio (INR) from 2.0 to 3.0 in 2012. In 2016 and 2020 an only 33% and 40.6% of patients achieved INR (2.0-3.0).Conclusion. Doctors have become more committed to following clinical guidelines during the period of the investigation. In 2020 antithrombotic therapy for atrial fibrillation was suitable according to current clinical guidelines

Efficacy and safety of the new oral anticoagulants in the treatment of venous thromboembolic complications: meta-analysis

Aim. Analysis of the efficacy and safety of the new oral anticoagulants (NOACs) in the management of venous thromboembolism (VTE).Material and methods. This meta-analysis of randomized controlled trials (RCTs) was made in accordance with the instructions “Preferred reporting items for systematic reviews and meta-analyses (PRISMA)”.Results. The meta-analysis included 5 RCTs. NOACs were as effective as vitamin K antagonists (VKAs) in preventing recurrent symptomatic VTE (RR=0.93; 95% CI 0.77-1.12; p=0.44). The incidence of recurrent thrombosis (RR=0.82; 95% CI 0.63-1.08; p=0.16) and deep vein thrombosis ± fatal or nonfatal pulmonary embolism (RR=1.06; 95% CI 0.81-1.40; p=0.66) was comparable in the groups of comparison. Meta-analysis of the safety of the NOACs suggested significant reduction of risk of major bleeding as compared with standard therapy (RR=0.54; 95% CI 0.42-0.69; р<0.00001). The incidence of all types of bleeding was significantly lower with NOACs (RR=0.70; 95% CI 0.51-0.95; p=0.02). All-cause mortality rate was comparable between the groups (RR=0.93; 95% CI 0.76-1.13; p=0.46).Conclusions. NOACs are as effective as the standard therapy, at that they are much safer in VTE treatment

Сравнение нескольких альтернативных режимов применения таргетных противоревматических препаратов в монотерапии раннего ревматоидного артрита

Objective: to evaluate the efficacy of tocilizumab (TCZ) versus tofacitinib (TOFA) in patients with severe and moderate rheumatoid arthritis (RA) who have not previously received methotrexate (MTX). Material and methods. A systematic search for studies dealing with the evaluation of the efficacy of TCZ and TOFA was made in accordance with the provisions of the instruction «Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)». Indirect comparison of two Function and ORAL Start randomized clinical trials was done, as described by Н.C. Buchera. The trials were comparable in their design and in the baseline characteristics of patients. The efficiency of pharmacotherapy for early RA was evaluated based on the ACR20/50/70 response rates in MTX-naive patients from three endpoints. Results. The indirect comparison of TOFA and TCZ (A MTX general control) after 52 weeks of treatment in MT-naive patients with severe and moderate RA indicated that the use of TOFA 5 mg twice daily and TCZ 8 mg/kg showed no difference in ACR20, ACR50, and ACR70 response rates. Nevertheless, there was a tendency to the greater efficiency of TOFA (5 mg twice daily) than that of TCZ (8 mg/kg). The indirect comparison of TOFA (10 mg twice daily) and TCZ (8 mg/kg) established that TCZ therapy was associated with the lower response rate for ACR50 (by 37%): the relative risk (RR) was 0.63; 95% confidence interval (CI), 0.44–0.90 and for ACR70 (by 51%): RR, 0.49; 95% CI, 0.29–0.83 as compared with TOFA therapy. Conclusion. The indirect comparisons confirmed that monotherapy with TOFA (10 mg twice daily) produced a more pronounced antiinflammatory effect than that with TCZ in MTX-naive patients with early severe and moderate RA of less than one year's duration. There were no statistically significant differences in ACR response rates between the TOFA (5 mg twice daily) and TCZ (8 mg/kg) groups. Цель исследования – оценить сравнительную эффективность тоцилизумаба (ТЦЗ) и тофацитиниба (ТОФА) у пациентов с тяжелым и среднетяжелым ревматоидным артритом (РА), которые ранее не получали метотрексат (МТ). Материал и методы. Выполнен систематический поиск исследований, посвященных оценке эффективности тоцилизумаба (ТЦЗ) и тофацитиниба (ТОФА), в соответствии с положениями инструкции «Предпочтительные параметры отчетности для систематических обзоров и метаанализа (PRISMA)». Проведено непрямое сравнение двух рандомизированных клинических исследований – Function и ORAL Start – по методике Н.С. Buchera. Исследования сопоставимы по дизайну и исходным характеристикам пациентов. Проанализирована эффективность фармакотерапии раннего РА по критериям ответа ACR20/50/70 у «МТ-наивных» пациентов, проведена оценка по трем конечным точкам. Результаты. Непрямое сравнение ТОФА и ТЦЗ (общий контроль – МТ) после 52 нед терапии у «МТ-наивных» пациентов с тяжелым и среднетяжелым РА показало, что при использовании ТОФА 5 мг 2 раза в сутки и ТЦЗ 8 мг/кг не наблюдается разницы в частоте достижения ответа по критериям ACR20, ACR50 и ACR70. Тем не менее прослеживается тенденция к большей эффективности ТОФА (5 мг 2 раза в сутки) по сравнению с ТЦЗ (8 мг/кг). При непрямом сравнении ТОФА (10 мг 2 раза в сутки) и ТЦЗ (8 мг/кг) установлено, что терапия ТЦЗ ассоциирована с более низкой частотой ответа по критериям ACR50 (на 37%): относительный риск (ОР) – 0,63; 95% доверительный интервал (ДИ) – 0,44–0,90 и ACR70 (на 51%): ОР – 0,49; 95% ДИ – 0,29–0,83 по сравнению ТОФА. Выводы. Результаты непрямого сравнения подтвердили, что более выраженным противовоспалительным эффектом монотерапии характеризуется ТОФА в дозе 10 мг 2 раза в сутки в сравнении с монотерапией ТЦЗ у пациентов с ранним (до 1 года) тяжелым и среднетяжелым РА, не получавших ранее МТ. Статистически значимых различий в эффективности ответа по критериям ACR между ТОФА (5 мг 2 раза в сутки) и ТЦЗ (8 мг/кг) не выявлено. 

Cutting Edge Geometry Effect on Plastic Deformation of Titanium Alloy

The paper presents experimental studies of ОТ4 titanium alloy machining with cutting edges of various geometry parameters. Experiments were performed at a low speed by the scheme of free cutting. Intensity of plastic shear strain was set for defining of cutting edge geometry effect on machining. Images of chip formed are shown. Estimation of strain magnitude was accomplished with digital image correlation method. Effect of rake angle and cutting edge angle has been studied. Depth of deformed layer and the area of the plastic strain is determine. Results showed that increasing the angle of the cutting edge inclination results in a change the mechanism of chip formation

Antibiotic Dosing in Chronic Kidney Disease

Infectious process is an important cause of morbidity and mortality among patients with chronic kidney disease. Prescription of antibacterial drugs should take into account the pharmacokinetic parameters of the medicine and the individual characteristics of the patient. Adequate antibiotic dosing is crucial for positive treatment outcome and minimisation of side effects. The aim of the study was to analyse scientific literature on factors affecting the dosing of antibacterials in patients with chronic kidney disease. Since most antibacterial medicines are eliminated by the kidneys, a decrease in glomerular filtration rate or kidney function should be followed by the dose adjustment in order to prevent the medicine accumulation and reduce the risk of side effects. Antibiotic dosing in such patients should be accompanied by kidney function assessment and be adjusted to ensure effective and safe treatment, as well as prevention of bacterial resistance. The review provides data on the dosing of some antibiotic groups (beta-lactams, aminoglycosides, fluoroquinolones) at different creatinine clearance rates. Extrarenal excretion of medicines does not usually require the dose adjustment in patients with chronic kidney disease

Эффективность и безопасность пероральных антикоагулянтов при венозных тромбоэмболических осложнениях: непрямые сравнения

Objective. The aim was to perform an indirect comparisons of the effectiveness and safety of new oral anticoagulants (NOACs) in the management of venous thromboembolism (VTE).Material and methods. In the absence of a head-to-head comparisons, indirect comparison was done using the method proposed by Butcher et al.Results. The indirect comparison included 5 RCTs. Apixaban, rivaroxaban and dabigatran were equally effective in preventing recurrent symptomatic VTE, deep vein thrombosis and pulmonary embolism. Dabigatran increased major bleeding risk compared to apixaban RR=2.36; 95% CI 1.15-4.82 and the risk major or clinical relevant non-major (CRNM) bleedings RR=1.43; 95% CI 1.06-1.93. Dabigatran and apixaban were associated with the significant lower risk of major and CRNM bleeding compared with rivaroxaban RR=1.49; 95% CI 1.17-1.91 and RR=2.13; 95% CI 1.66-2.74.Conclusions. There were no statistically significant differences between apixaban, dabigatran and rivaroxaban in effectiveness. Apixaban treatment associated with the most favorable safety profile of the NOACs.Цель исследования – провести сравнительный анализ эффективности и безопасности новых пероральных антикоагулянтов (ривароксабана, дабигатрана и апиксабана) со стандартной терапией венозных тромбоэмболических осложнений (ВТЭО).Материалы и методы. Проведены непрямые сравнения новых пероральных антикоагулянтов.Результаты. Для выполнения непрямого сравнения включено пять рандомизированных контролируемых испытаний (РКИ). Статистически достоверных различий между тремя новыми антикоагулянтами (ривароксабан, дабигатран, апиксабан) для исходов, оценивающих эффективность, включая ВТЭО, тромбоз глубоких вен и тромбоэмболию легочной артерии, не выявлено. Риск развития массивных кровотечений на фоне терапии дабигатраном выше, чем в случае назначения апиксабана ОР=2,36; 95% ДИ 1,15-4,82. В сравнении с дабигатраном апиксабан достоверно реже вызывает все клинически значимые кровотечения (ОР=1,43; 95% ДИ 1,06-1,93). При непрямом сравнении по конечной точке комбинации всех клинически значимых кровотечений ривароксабан уступает дабигатрану и апиксабану (ОР=1,49; 95% ДИ 1,17-1,91 и ОР=2,13; 95% ДИ 1,66-2,74 соответственно).Заключение. При сопоставимой эффективности ривароксабана, дабигатрана и апиксабана последний обладает более благоприятным профилем безопасности (по частоте геморрагических осложнений) из зарегистрированных в настоящее время препаратов данной группы