Orenburg,, Russian Federation

Russian Registry of Surgical OutcomeS

Currently, the incidence of perioperative complications and mortality associated with surgical intervention are minimized. However, taking into account the significant number of surgical interventions performed worldwide (more than 300 million per year), the total number of patients with complicated postoperative periods is large, and postoperative mortality ranks third in the structure of causes of death (7, 7%), second only to coronary heart disease and stroke. Moreover, even in discharged patients, complications that develop can significantly reduce quality of life and worsen long-term prognosis. To a greater extent, the above applies to high-risk patients, whose identification is a priority task of anesthesiology. Identification of risk factors that cause a high probability of an unfavorable outcome is currently unthinkable without conducting comprehensive prospective population-based studies, which, on the one hand, make it possible to assess the contribution of many variables to the risk of complications and mortality, and on the other hand, to maximally cover a certain population by identifying characteristic predictors for it. To date, several population-based studies and programs have been described in the literature that have led to the creation of national databases (registries) of postoperative outcomes. Such studies include several international (ISOS, EuSOS and ASOS) and national ones, such as SweSOS [8] or ColSOS , which are at different stages of implementation. Among the national databases, the best known is the ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database, which contains information on the outcomes of surgical treatment for more than 5 million patients in the United States since 1991 . The results obtained from these studies often vary widely, due to the diversity of approaches to study inclusion criteria, differences in the characteristics of the populations studied, and the lack of a uniform view on the classification of postoperative outcomes. When assessing mortality, the authors most often record 30-day mortality, however, taking into account modern ideas about the role of perioperative factors and complications in the development of an unfavorable long-term outcome, the need to determine one-year mortality becomes obvious. As shown by the national observational study SweSOS, the mortality rate increases significantly over time, with 30-day mortality being 1.8%, 3-month mortality - 3.9%, and 6-month and annual mortality - 5.0% and 8.5% , respectively . There is also no uniform approach to the registration of postoperative complications, and modern protocols use several systems, the most common of which are the classification of the joint working group of ESA (The European Society of Anesthesiologists) and ESICM (The European Society of Intensive Care Medicine, The European). Society of Intensive Care Medicine) and the ACS-NSQIP classification (The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP)). And although they are similar in many ways (complications are grouped into blocks according to the nature of the disorders), differences are also present, and even the same complication may have a different definition. In addition, some significant outcomes are not included in these classifications, which predetermines their underestimation. Of course, one of the advantages of creating a large population-based database is the recording of a large number of potential predictors of adverse outcome and subsequent assessment of their individual contribution to the complex perioperative risk. The type of surgical intervention itself is a factor that largely determines the likelihood of complications. The goal is to create a Russian national calculator for the risk of postoperative complications and mortality. Primary target points: 1. Creation of a national register of postoperative outcomes in different areas of surgery. 2. Determination of the frequency and structure of outcomes after elective and emergency surgery. 3. Identification of predictors of unfavorable outcome. 4. Development and validation of a model for predicting complications and mortality in various areas of surgery 5. Creation of calculators for the risk of postoperative complications and mortality in various fields of surgery and their integration into a single calculator 6. Analysis of long-term results in patients with postoperative complications (90 days and a year after surgery) Secondary target points: 1. The role of concomitant diseases in the development of unfavorable outcome 2. The influence of age on primary and secondary postoperative outcomes 3. The influence of the type of anesthesia on the course of the postoperative period 4. The influence of oncological pathology and specific treatment on primary and secondary postoperative outcomes 5. The impact of the urgency of surgery on the risk of an unfavorable outcome 6. Influence of localization, access and duration of surgery on postoperative outcome 7. Assessment and validation of surgical and anesthesiological risk scales for lethal outcome (can be listed) 8. Evaluation and validation of surgical and anesthetic risk scales for primary and secondary outcomes 9. Stratification of patients at high perioperative risk with details on cardiac, respiratory, neurological, renal, hepatic, hemostasiological, infectious and others. 10. Influence of quality criteria for implementation of FAR recommendations on the course of the postoperative period 11. Analysis of the course of ICU-syndrome in patients with complications and depending on the maximum score on the SOFA scale and the structure of MOF in the postoperative period 12. Analysis of the effectiveness of rehabilitation measures in patients with ICU-syndrome 13. Analysis of the causes of mortality (based on autopsy reports and clinical and laboratory data of patients). Cohort A The checklist (basic) is filled out for all patients with postoperative complications. At the same time, the total number of patients operated on in a particular center is taken into account on a quarterly basis, taking into account their distribution by area of surgery. Based on the data from the basic checklist, answers will be received to the following target points: 1. Creation of a national register of postoperative outcomes in different areas of surgery. 2. Determination of the frequency and structure of outcomes after planned and emergency surgical interventions. 3. Analysis of long-term results in patients with postoperative complications (90 days and a year after surgery) 4. Analysis of the course of ICU-syndrome in patients with complications and depending on the maximum score on the scale and the structure of MOF in the postoperative period 5. Analysis of the effectiveness of rehabilitation measures in patients with ICU syndrome Cohort B Basic checklist plus additional checklist: completed for all operated patients within one selected week quarterly The total number of patients operated on in a particular center is also taken into account quarterly, taking into account their distribution by area of surgery. Based on the data from the basic and additional checklists, answers to the most important target points (3 primary and 10 secondary) will be obtained: 1. Identification of predictors of unfavorable outcome. 2. Development and validation of a model for predicting complications and mortality in various fields of surgery 3. Creation of calculators for the risk of postoperative complications and mortality in various fields of surgery and their integration into a single calculator 4. The role of concomitant diseases in the development of unfavorable outcome 5. The influence of age on primary and secondary postoperative outcomes 6. The influence of the type of anesthesia on the course of the postoperative period 7. The influence of oncological pathology and specific treatment on primary and secondary postoperative outcomes 8. The impact of the urgency of surgery on the risk of an unfavorable outcome 9. The influence of localization, access and duration of surgery on postoperative outcome 10. Assessment and validation of surgical and anesthesiological risk scales for lethal outcome (can be listed) 11. Evaluation and validation of surgical and anesthetic risk scales for primary and secondary outcomes 12. Stratification of patients at high perioperative risk with details on cardiac, respiratory, neurological, renal, hepatic, hemostasiological, infectious and others. 13. Influence of quality criteria for implementation of FAR recommendations on the course of the postoperative period

HER2-low Unresectable and/or Metastatic Breast Cancer in Russia

Clinical and demOgRaphic Features of Patients With Uncontrolled Severe Asthma in Russia (CORSAR)

There are limited epidemiological data of the patients with uncontrolled severe asthma in Russia since there is no unified system for regular monitoring of patients with severe asthma in the country. The systematic information about complications and comorbidities, about the treatment approaches and their effectiveness in the Russian population is also absent. The observational registry is really important to describe the epidemiological characteristics of the disease and to analyse the clinical characteristics of the various subgroups of patients. This is an excellent starting point to be able to investigate the characteristics of the disease in detail. The Russian Federation consists of 85 regions with a total population of more than 145 million people. The regions differ in ethnic composition, age, gender, climate, ecology, economic level, prevalence of asthma in general and severe asthma in particular. Previously reported observational registries are International Severe Asthma Registry (ISAR) and Russian Severe Asthma Registry (RSAR), both studies included patients regardless of whether patients received biological agents or not. The percentage of patients receiving biologics in these studies was 25.4% and 10.6% respectively. Thus, there is a need to perform a large-scale observational registry in regions of the country with a sufficient size of population to obtain information on SA epidemiology, clinical and demographic characteristics, to describe main clinical outcomes and evaluate existing associations between observed treatment patterns and clinical outcomes in real clinical practice in patients with uncontrolled SA not receiving biologic therapy. Trial will have cross-sectional design and will include 1 visit for obtaining the patient's demographic and clinical data. To allow wide data coverage the study will involve at least 50 regions of Russian Federation; in each region 100 patients will be recruited. The total size of study population will be 5 000 patients.

Real-world Study Assessing Efficacy of TezepeLumaB in Patients With Severe Asthma Regardless of Phenotype in Russia

This is a multi-centre, retrospective-prospective, non-comparative and non-interventional (observational) cohort study involving primary and secondary data collection within real-world settings of participants who initiate tezepelumab for treatment of severe uncontrolled asthma. Participants of the study will be the patients eligible for tezepelumab treatment based on the assessment in accordance with the approved product Summary of Product Characteristics (SmPC) in Russia. The administration of tezepelumab will be independent of this study (i.e., a decision of tezepelumab initiation is based on the physician's choice and regulatory and clinical features, not on recruitment/participation in the study). Tezepelumab is indicated as an add-on maintenance treatment for severe asthma, therefore, patients will continue background asthma therapy throughout the study, irrespective of their decision to participate in this study or not. 110 eligible participants of both sexes, aged 12 years or older will be treated with tezepelumab available in the market and according to the Russian reimbursement policies in approximately 20 sites. In eligible participants who agree to take part in the study, the enrolment date is defined as the date of informed consent or assent. After enrolment and evaluation of inclusion/exclusion criteria, study participants will commence tezepelumab treatment as per the physician's decision and following the local product SmPC. The index date is defined as the date when participants have received the first dose of tezepelumab. The enrolment period is the period between enrolment date and index date. Additionally, participants may be enrolled in this study up to 4 weeks after the first dose of tezepelumab, but no longer, to avoid responder bias. Participants will be followed for a maximum period of 52 weeks after index date, irrespective of treatment discontinuation. Patient-reported outcomes - the primary endpoint (ACQ-5) and SNOT-22 will be retrospectively collected during enrolment for all patients (i.e. the most recent available values in the 52 weeks prior to index date), and prospectively collected at suggested visits at Weeks 4, 12, 24, and 52 following index date. For patients who initiate treatment after being enrolled into the study the baseline value may be collected prospectively after enrolment before start of treatment. The baseline period is defined as the 52 weeks prior to the index date. Outcomes of interest, such as severe asthma exacerbations, medication use, and healthcare resource utilization, will be collected during enrolment retrospectively for the baseline period (52 weeks prior to the index date) and then prospectively at Weeks 4, 12, 24, and 52 following index date. Overall expected duration of the study (from the first patient inclusion to the last patient last visit) is about 2 years or until 110 eligible patients are included to the study and data on these patients are collected, whichever occurs first. As an observational, this study does not imply any intervention into a routine clinical practice, including choice of treatment modality or additional diagnostic methods.

Clinical& Demographic Profiles of patIents With unControllEd Asthma in Russia: Multi-center oBsErvational ReGistry Study

There are limited epidemiological data of the patients with uncontrolled asthma in Russia. The systematic information about complications and comorbidities, about the treatment approaches and their effectiveness in the Russian population is also absent. The observational registry is really important to describe the epidemiological characteristics of the disease and to analyse the clinical characteristics of the various subgroups of patients. This is an excellent starting point to be able to investigate the characteristics of the disease in detail. The Russian Federation consists of 85 regions with a total population of more than 145 million people. The regions differ in ethnic composition, age, gender, climate, ecology, economic level, prevalence of asthma in general and uncontrolled asthma in particular. Thus, there is a need to perform a large-scale observational registry in regions of the country with a sufficient size of population to obtain information on uncontrolled asthma epidemiology, clinical and demographic characteristics, to describe main clinical outcomes and evaluate existing associations between observed treatment patterns and clinical outcomes in real clinical practice in patients with uncontrolled asthma not receiving biologic therapy. Trial will have ambispective design and will include 2 visits for obtaining the patient's demographic and clinical data. To allow wide data coverage the study will involve at least 50 regions of Russian Federation; in each region 200 patients will be recruited. The total size of study population will be 10 000 patients. All data will be collected during 2 visits carried out according to routine clinical practice for observation and treatment of patients with uncontrolled asthma. At visit 1, baseline data of 52 weeks prior to inclusion will be collected by physician based on the patient's medical records and interview during the visit. Visit 2 (final visit) will be conducted after 3 months in order to collect follow-up data which coincides with the recommended dates. Information on changes in the treatment of uncontrolled asthma and on clinical outcomes will be collected. This non-interventional study does not imply any intervention into a routine clinical practice, and does not provide for any diagnostic and therapeutic procedures other than those used in routine practice.

An Efficacy and Safety Study of GNR-086 (canakinumab Biosimilar) and Ilaris® in Patients with Adult-onset Still's Disease

GNR-086 is being developed as a proposed biosimilar to Ilaris®, a lyophilisate for the preparation of a solution for subcutaneous administration. Canakinumab is a fully human monoclonal antibody of the immuniglobulin G1 (IgG1(kappa)) isotype that binds specifically and with high affinity to interleukin-1β (IL-1β). Canakinumab, by binding to human IL-1β, blocks the interaction of this cytokine with its receptors, thereby functionally neutralizing the biological activity of this cytokine, without preventing either the binding of the natural inhibitor IL-1Ra, or the binding of IL-1α to IL-1 receptors. IL-1β is recognized as one of the main pro-inflammatory cytokines in various inflammatory conditions. This III phase study is aimed to compare the efficacy, safety and immunogenicity of GNR-086 and Ilaris®. The study will enroll patients with the confirmed diagnosis of adult-onset Still's disease in accordance with the classification criteria of Yamaguchi M. et al. (J. Rheumatology, 1992), and the duration of the disease at least 2 months before inclusion into the study. 148 paitnts will be randomised 2:1 to receive either GNR-098 or Ilaris®. Participants will receive canakinumab 4 mg/kg suncutaneously every 4 weeks for 24 weeks following the study extension.

Clinical and Demographic Features of Patients With Moderate to Severe Active Systemic Lupus Erythematosus in Russia

Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease with variable clinical manifestations and an unpredictable course, affecting any organs or systems, which quite often develops over several months or years, with persistent or, conversely, rapidly changing clinical manifestations, an undulating course, alternating remissions and flares. Currently, in Russia there is no exact data on the number of patients with active moderate to severe SLE in the population, since there is no unified system for regular monitoring of patients with SLE in the country. The systematic information about complications and comorbidities, about the treatment approaches and their effectiveness in the Russian population is also absent. The Russian Federation consists of 85 regions with a total population of more than 145 million people. The regions differ in ethnic composition, age, gender, climate, ecology, economic level, prevalence of SLE in general and moderate to severe SLE in particular. Thus, there is a need to perform a large-scale observational study in regions of the country with a sufficient size of population to obtain information on moderate to severe SLE epidemiology, clinical and demographic characteristics, to describe main clinical outcomes and evaluate existing associations between observed treatment patterns and clinical outcomes in real clinical practice. Trial will include 2 visits for obtaining the patient's demographic and clinical data: the 1st is retrospective and the 2nd is prospective. To allow wide data coverage the study will involve approximately 50 sites of Russian Federation; in each site about 20 patients will be recruited. Overall expected duration of the study (from the first patient inclusion to the last patient last visit) is about 13 months or until 1000 patients will be included in the retrospective phase and ~ 600 patients - in the prospective phase This observational study does not imply any intervention into a routine clinical practice, including choice of treatment modality or special methods of investigation.

Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis

This is a Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of anifrolumab versus placebo as added to SOC (consisting of MMF and glucocorticoids) in adults with active proliferative Class III or Class IV LN (both with or without concomitant Class V). The total study duration may be up to approximately 116 weeks, including the Screening and Follow-up. Approximately 360 participants will be randomized in a 1:1 ratio to receive anifrolumab or matching placebo throughout during the Treatment Period.

CLL Therapy Approaches in Russia

The Role of Concomitant Diseases in Postoperative Complications Risk Stratification.

Advances in modern anesthesiology have significantly reduced the risk of anesthesia compared to the last century, however, the level of perioperative hospital mortality of planned operations at the moment is on average about 0.5% (ISOS group, 2016). Weiser et al. (2016) estimated that more than 313 million adults worldwide are subject to surgery each year. Thus, the number of deaths may result in several million each year worldwide. However, the study of the mortality risk is associated with certain difficulties, because over the past half century, this figure has decreased a hundred times and the study requires studies that include a large number of participants. Current research focuses on other outcome criteria - postoperative complications. Thus, anesthetic risk often refers to the risk of postoperative complications. The frequency of these complications varies in a wide range, ranging from 3 to 18 % (Gawande AA, 1999, Kable AK, 2002, Malik OS, 2018). The differences in the data are explained by the lack of clear definitions and differences in the design of studies, but the fact that the development of postoperative complications increases the risk of death several times (ISOS group, 2016) can be considered undoubted. However, despite the importance of this issue, in modern literature there is no clear idea of what is considered a high risk and which of the patients corresponds to this category. Understanding whether a patient is at high risk is an essential task - it allows you to obtain meaningful informed consent of the patient, as well as to understand whether to apply strategies for the prevention of complications (targeted infusion therapy, protective respiratory support, especially monitoring in the postoperative period, etc.). Attempts at preoperative risk stratification have been made for many decades, some scales estimate the initial physical status (ASA scale) (Young J, 2015) and predict mortality, others estimate the risk of specific complications (Lee index, respiratory risk scale, etc.) . Scales including intraoperative and postoperative parameters such as the POSSUM series of scales (Whiteley MS, 1996) are also being developed. The analysis shows that in routine clinical practice, these scales are not used very often, due to their limitations: subjectivity, technical complexity and often - low specificity and sensitivity. Concomitant diseases are the strongest predictors of postoperative adverse events and annual mortality. Monk et al. (2005) demonstrated that Charlson's comorbidity score of 3 or more significantly increased the risk of death. In addition, in most clinical studies, the ASAclassification of physical status as a kind of comprehensive assessment of patient comorbidity has repeatedly proved to be one of the strongest independent predictors of postoperative morbidity and mortality, despite the fact that this assessment is based on subjective perception (Watt J., 2018). The main concomitant diseases that are independent predictors of perioperative complications are diseases of the cardiovascular and respiratory systems (Van Diepen S, 2011). Increasing age, anemia, obesity, diabetes - these conditions also increase the risk of an adverse outcome. Diseases of the Central nervous system and neuromuscular diseases significantly disrupt the function of respiration, can change the level of the Autonomous regulation of the cardiovascular system, lead to significant cognitive disorders and nutritional deficiency, which also increases the risk of perioperative complications (Hachenberg T, 2014). On the other hand, large-scale observational studies conducted in recent years in a number of countries have not identified comorbidities as independent predictors of postoperative complications (Malik, 2018). Thus, data on the risk effects of comorbidities are contradictory and may be influenced by differences in the frequency and structure of these diseases in heterogeneous populations, as well as in different treatment strategies for cardiovascular, respiratory and other diseases. The identification of these risk factors is necessary to understand the pathophysiology of complications and identify potential ways to reduce anesthetic risk, such as the correction of concomitant disease. The degree of risk of surgery, of course, depends not only on the presence of comorbidities and their combinations, but also on the severity of surgical injury (Pearse RM, 2012, ISOS group, 2017), as well as the level of exposure to drugs for anesthesia and anesthetic techniques (Malik OS, 2018), therefore, the allocation of risk groups without these factors is also not appropriate. Objective: to assess the frequency and structure of comorbidities in patients undergoing surgery on the abdominal organs and to stratify the risk of postoperative complications by determining independent Evaluated parameters in study: 1. Age, gender; 2. Class of physical status by ASA; 3. The presence and type of concomitant disease; 3.1 CHD; 3.2 CHF; 3.3 Heart rhythm disorders; 3.4 COPD; 3.5 Bronchial Asthma; 3.6 CKD; 3.7 CNS diseases; 3.7.1 Stroke; 3.7.2 Epilepsy; 3.7.3 Parkinson's Disease; 3.7.4 Alzheimer's Disease; 3.8 Neuromuscular diseases; 3.9 Diabetes; 3.10 Anemia; 4 Treatment received by the patient; 4.1 β-blockers; 4.2 ACE Inhibitors; 4.3 Aldosterone antagonists; 4.4 Statins; 4.5 Anticoagulants; 4.6 Diuretics; 4.7 Bronchodilators; 4.8 Corticosteriods; 4.9 Insulin; 4.10 Anticonvulsants; 5. The type and severity of surgery ; 5.1 Open surgery on the organs of the upper abdomen; 5.2 Coloproctological operations; 5.3 Gynecological surgery; 5.4 Urological surgery; 5.5 Operations on vessels of the abdominal cavity; 5.6 Abdominal wall surgery; 5.7 Laparoscopic surgery; 6 Type of anesthesia; 6.1 Spinal; 6.2 Epidural; 6.3 Combined spinal-epidural; 6.4 Intravenous; 6.5 Combined; 6.6 General+epidural; 7. Integral scales; 7.1 The cognitive function of the Montreal scale ; 7.2 Respiratory risk ; 7.3 Lee's Cardiovascular Risk Scale ; 7.4 NSQIP Cardiac risk scale ; 7.5 Hepatic insufficiency according to MELD; 7.6 CKD Stage by Level of GFR and Albuminuria; 7.7 COPD degree by GOLD. Order of conduct 1. The data is registered in the Excel electronic database in a uniform format for all centers (the form will be sent by the coordinator to all centers participating in the study prior to the inclusion of patients). 2. All centers need to get approval by the local ethics committee before the start of the study. The study protocol will be registered in Clinicaltrial.gov. 3. The study includes all patients operated on within one operational day at the discretion of the center and meeting the inclusion criteria with registration in the questionnaire of the day of the week. 4. All patients could sign informed consent to participate in the study prior to inclusion in the study. 5. Before surgery, data on the patient and all studied factors specified in the study protocol are entered into the database. 6. All patients included in the study are monitored before discharge from the hospital with registration of the data specified in the protocol. 6. Every last day of the working week, all completed cases are sent as a separate Excel file to the study coordinator by email to trembachnv@mail.ru 7. The originals of the questionnaires are stored in the centers for the entire study time and for 3 years after its completion. 8. The summary database is formed by the study coordinator and provided to the centers after the end of the study. Statistical analysis The sample size was calculated taking into account the fact that at least 10 cases of postoperative complications per one factor included in the final regression model are required. Given the wide range of complication rates in previous studies (from 3% to 20%), we have chosen a lower bound for a more accurate assessment. To include 20 potential risk factors in the regression model, 200 cases of postoperative complications are required, which at a frequency of 3% is not less than 7000 people. Taking into account the risk of data loss, and taking into account as many potential risk factors as possible, the size of the required sample was increased to 12,000 people, which will also assess the contribution of comorbidities to certain groups of complications. For validation of predictive models will be recruited 4,000 additional. The inclusion of the patient in the main and validation group will be carried out randomly. The character of distribution of studied parameters will be evaluated using the criterion Kolmogorov-Smirnov. The continuous data will be presented as the median and interquartile range for the nonparametric distribution and as the mean and standard deviation for the parametric distribution. Categorical variables will be presented as the number of patients and a percentage of the total number of patients. For the initial assessment of the Association of the factor with postoperative complications, a single-factor analysis using the χ2 criterion and the Mann-Whitney test will be carried out. All variables with a reliable relationship identified in the univariate analysis (p less than 0.05) will be included in logistic regression if there is no collinearity between them (correlation coefficient less than 0.25). The logistic regression model will be constructed using a step-by-step reverse inclusion procedure in which the presence of a complication will be a dependent variable. Potential predictors will be removed if this exception does not cause a significant change in the log likelihood ratio. The criterion for excluding the factor will be set at the significance level of 0.05. Adjusted odds ratios and 95% confidence intervals will also be calculated. The resulting predictive model will be evaluated in the validation group using ROC analysis and the Hosmer-Lemeshov test.