Real Clinical Practice In Patients Research Articles

Risk of Death and Heart Failure among Patients with Type 2 Diabetes Treated by Metformin and Nonmetformin Monotherapy: A Real-World Study.

Background To assess the association of metformin monotherapy with the risk of all-cause deaths and cardiovascular deaths and events in type 2 diabetes patients in real clinical practice. Methods This retrospective, observational study comprised patients with type 2 diabetes initially treated with metformin or nonmetformin monotherapy over 2011-2016. Data were extracted from the National Healthcare Big Data database in Fuzhou, China. Propensity score matching (PSM) was performed, matching each patient on metformin to one on nonmetformin in terms of a set of covariates. The primary endpoint was all-cause death, and secondary endpoints were cardiovascular death, heart failure, and heart failure hospitalization. Covariate-adjusted associations of metformin use with all the endpoints were assessed by Cox proportional hazards models. Results Among 24,099 patients, 5491 were initially treated with metformin and 18,608 with nonmetformin. PSM yielded 5482 patients in each cohort. During a median follow-up of 2.02 years, we observed 110 and 211 deaths in the metformin and nonmetformin groups, respectively. Metformin was significantly associated with reduced risk of all-cause death (adjusted hazard ratio (aHR) 0.52, 95% confidence interval (CI) 0.39-0.69), cardiovascular death (aHR 0.63, 95% CI 0.43-0.91), and heart failure (aHR 0.61, 95% CI 0.52-0.73), whereas the reduced risk in heart failure hospitalization was not statistically significant (aHR 0.70, 95% CI 0.47-1.02). Conclusions In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications.

Surrogates of response to treatment of non-small cell lung cancer with immunotherapy: Toxicity and leukocyte ratios—Experience of a center.

e21052 Background: Immunotherapy is proposed as a therapeutic novelty in metastatic non-small cell lung cancer (NSCLC), in many cases already in front line. It presents different adverse effects than traditional schemes, due to the stimulation of the immune system. There is a possible relationship between toxicity and response. Neutrophil-to-lymphocyte ratio (NLR) as a possible predictive factor of response. Objectives: Evaluating the response according to the toxicity degree in NSCLC patients in real clinical practice. Analyze whether pretreatment NLR high patients have a worse prognosis. Methods: Observational, retrospective, analytical, single-center study. HCULB stage IV NSCLC patients with inmunotherapy treatment during 2016-2018. Descriptive and multivariate analysis. Toxicity grade: CTCAE version 4.0. Response assessment: RECIST 2.0 and immunorelated criteria. Toxicity degree and response (global and individualized results according to treatment and histology). Neutrophil-to-lymphocyte ratio and response. Results: N = 43 patients (35 men, 8 women). Average age 64 years. Response: 3 complete response (CR) (toxicity ≥2), 13 partial response (PR) (toxicity ≥1), 13 stable disease (SD), 12 progression (P) (only 4 toxicity and ≤2), 2 not evaluated. Hypothyroidism as the most common irAE. Relationship between toxicity and response: the absence of irAEs conditions worse prognosis p < 0.05. Histology: 25 adenocarcinoma [18 with irAES (1 CR, 7 PR, 8 SD,) and 7 without (1 SD, 5 P, 1 no ev.)]; 17 squamous [13 with irAES (1 CR, 6 PR, 4 SD) and 4 without (3 P, 1 no ev.)]; 1 adenosquamous with irAES and CR. Drug: Atezolizumab N = 8 [6 with irAES (2 PR, 3 SD, 1 P) and 2 without (both P)], Nivolumab N = 16 [9 with irAES (1 CR, 3 PR, 3 SD, 2 P) and 7 without (1 SD, 4 P, 2 no ev.)], Pembrolizumab N = 19 [17 with irAEs (2 CR, 8 PR, 6 SD, 1 P) and 2 without (both P)]. Significant positive correlation between toxicity and response (p < 0.001) R = 0.067, (CI 99% 0.378-0.837), regardless of histology and drug. It is observed a better response in those patients who presented a NRL close to 3 or less at the beginning of treatment. On the contrary, it is observed that subjects with NRL greater than 4 obtained worse results when they were treated with immunotherapy. Conclusions: The appearance of irAES like a response indicator of immune system, seem to conditione better evolution. In contrast, the absence of toxicity predicts a worse prognosis. Further studies with a larger sample are needed to confirm our findings about the predictive value of NLR and optimize therapeutic regimens if necessary.

Comparative effectiveness of various immunosuppressive therapy regimens for uveitis in patients with Behçet’s disease

The aim – to evaluate the effectiveness of various immunosuppressive therapy schemes for current uveitis used in real clinical practice in patients with Behçet’s disease (BD).Material and methods. The study included 531 patients with a reliable (ICBD criteria 2014) diagnosis of BD, observed in the V.A. Nasonova Research Institute of Rheumatology from 2006 to 2020. The majority were men (331 (62.3%)). The average age (M±SD) was 32.9±10.0 years, the median duration of BD (Me (25%; 75%)) – 96 (48; 174) months. 60.4% patients had uveitis, 70.7% – exacerbation of uveitis (EU). Uveitis activity was assessed by the BOS24 index (Behçet’s disease Ocular attack Score 24) in 202 patients with EU. The total activity of BD was evaluated according to BDCAF index (Behçet’s Disease Current Activity Form). Glucocorticoids (GC) was systematically received by 68.7% patients with EU, including 51.5% in the form of pulse therapy. 88.9% patients with EU received cytotoxics: 33.5% – cyclosporine (CS), 20.7% – azathioprine (AZA), 11.4% – AZA+COL, 8.8% – AZA+CS, 7.5% – colchicine (COL), 3.9% – cyclophosphamide (CPh). 11.9% patients with EU were prescribe Biologics, mainly i-TNF-α (11,4%: 8,8% – adalimumab, 2.2% – infliximab, 0.4% – golimumab) and rituximab (0.4%). The effectiveness of therapy was evaluated on average after 18.0 (8.0; 36.0) months.Results. According to the dynamics of BDCAF, by the end of follow-up, BD activity significantly decreased in all groups, with the exception of patients who received COL. A more significant decrease in BDCAF was observed in the combination therapy groups: AZA+CS (ΔBDCAF=–4.08±3.60), AZA+COL (ΔBDCAF=–3.57±2.50), as well as in the CS group (ΔBDCAF=–3.57±3.39), but no statistically significant differences in ΔBDCAF between the groups were obtained, which does not allow us to speak about a significant advantage of a particular drug. There were no significant differences in ΔBDCAF between patients who received (ΔBDCAF=–3.41±3.89) and those who did not receive (ΔBDCAF=–3.59±3.23) Biologics. According to the dynamics of BOS24, the most effective for relieving symptoms of intraocular inflammation were CS (ΔBOS24=–7.0 (–12.0; –3.0)), AZA (ΔBOS24=–7.0 (–15.0; –2.0)), a combination of CS+AZA (ΔBOS24=–5.0 (–8.0; –2.0)) and CPh (ΔBOS24=–4.0 (–14.0; –2.0). The differences between BOS24 before and after treatment in these groups were statistically significant. When assigning AZA+COL (ΔBOS24=–1.0 (–4.0; 0)) or COL (ΔBOS24=–0.5 (–2.0; 0)) uveitis activity decreased during therapy, but not significantly. According to ΔBOS24, uveitis therapy by CS was statistically significantly more effective compared to AZA+COL and COL; and AZA treatment, compared to COL. Biologics, mainly adalimumab, significantly and rapidly reduce the severity of intraocular inflammation (ΔBOS24=–7.0 (–18.0; 0)) compared with GC and cytotoxics (ΔBOS24=–4,0 (–9,0; –1,0)), however statistically significant differences between the groups were not obtained due to the small number of Biologics groups.Conclusion. CS, AZA and their combination, as well as i-TNF-α (mainly adalimumab) are more effective for relieving uveitis symptoms in patients with BD. BOS24 is a reliable tool for quantifying the activity of uveitis in BD patients and its dynamics against the background of anti-inflammatory and immunosuppressive therapy.

ASSESSMENT OF THE FREQUENCY AND RATIONALITY OF PRESCRIBED MEDICINES IN PATIENTS WITH LIVER CIRRHOSIS

The aim. Assessment of the dynamics of prescribing drugs to patients with liver cirrhosis (LC, K 74), in terms of real clinical practice by methods of clinical and economic analysis.
 Materials and methods. 355 medical cards of inpatients with cirrhosis of the liver, which were divided into 4 groups depending on the period of stay of patients in the hospital. Methods: compatible retrospective ABC-frequency analysis, which ranked drugs consumed by patients in real clinical practice, according to the frequency of appointment using ABC-segmentation according to the Pareto principle (A – 80 % of drugs appointments: B – 15 %: C – 5 %); VEN-analysis, which divides the consumed drugs on a formal basis depending on the presence / absence of a particular drug in the regulations: vital (Vital or V), necessary (Essential or E) and secondary (Non-essential or N).
 Results. Cirrhosis of the liver in recent years has been on the 10th - 11th place among the causes of death in the world. The analysis of prescribed drugs to patients with LC in real clinical practice in Ivano-Frankivsk region of Ukraine revealed that over the years doctors prescribed fewer drugs on average per patient (11.4 drugs → 8.8 drugs), which can be considered a positive fact. Among the prescribed drugs, drugs of group A – “Drugs that affect the digestive system and metabolism” prevailed, the share of which increased and was the highest in 2019 – 2020 (2007–2009 – 44.6 %; 2012–2013 – 46.6 %; 2015–2016 – 48.1 %; 2019–2020 – 48.55 %); the share of dietary supplements also increased from 1.65 % to 6.52 %.
 Conclusions. Combined ABC-frequency and VEN-analyzes showed that the leaders in the years of hospital stay were the following drugs: Sodium chloride, Ademetionine, Pantoprazole, Spironolactone, Thioctic acid, Ornithine, Asparaginate K-Mg, Torasemide, Furosemide. However, the vital class V included only 9–11 % of drugs from the whole set of prescribed drugs, which requires systemic correction in accordance with European recommendations.

Субпопуляции Т-хелперов, ключевые цитокины и хемокины в патогенезе воспалительных заболеваний кишечника (часть 2)*

Studies in recent decades have identified the role of various T-helper cell subsets in the pathogenesis of inflammatory bowel diseases (IBD) and have shown the importance of cytokine-mediated regulation of the immune response in patients with ulcerative colitis (UC) and Crohn’s disease (CD). The imbalance between pro-inflammatory and anti-inflammatory cytokines in IBD prevents resolution of inflammation and leads to chronic course, disease progression and tissue destruction. In the review article, the role of key cytokines that are important in the development and progression of IBD is discussed. Of the pro-inflammatory mediators involved in the pathogenesis of IBD, special attention is currently paid to chemokines – cytokines belonging to chemoattractants. Chemokines are responsible for directed migration and attraction of cells expressing a certain set of receptors to organs, tissues and foci of inflammation. The article provides unique data on the importance of some chemokines in IBD. Cytokines, chemokines and their receptors are considered as potential therapeutic targets in IBD. Cytokine-targeted therapy using antibodies against TNF-α and antibodies to IL-12/IL-23 have already shown high efficiency and safety in randomized clinical trials, as well as in real clinical practice in patients with IBD. The data presented by the authors are important for clarifying the role of immunological processes, including microbiome-dependent ones, in the etiopathogenesis of IBD. Key words: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, T-helper cell subsets, cytokines, chemokines, gut microbiome

Лечение коморбидных пациентов с дислипидемией в реальной клинической практике: возможности питавастатина

This paper summarizes international clinical experience with the next generation of statins, pitavastatin, in dyslipidemias. This medication is effective at a dose of 1–4 mg in most patients (including comorbid patients) compared to other statins. Pitavastatin affects various parameters of the lipid profile (i.e., total cholesterol, high-density, low-density, and very-low-density lipoprotein cholesterol, triglycerides, apolipoproteins) and provides pleotropic effects (plaque stabilization, reduction in the levels of systemic inflammatory markers, antithrombotic and antidiabetic effects etc.). The unique structure of this medication and its metabolism account for the minimal risk of adverse effects (AEs) or drug interactions. Hence, pitavastatin is recommended for elderly and senile patients with senile asthenia, patients receiving multiple therapies or individuals with intolerance to other statins. Pitavastatin is prescribed as monotherapy or along with ezetimibe. Long-term taking is associated with the reduction in the rate of cardiovascular events and minimal AEs. This case report (a 65-year-old woman with dyslipidemia, comorbidities, and high cardiovascular risk) illustrates the efficacy and safety of pitavastatin. KEYWORDS: dyslipidemia, hypercholesterolemia, comorbidity, lipid-lowering therapy, high cardiovascular risk. FOR CITATION: Sedykh D.Yu., Khryachkova O.N., Kashtalap V.V., Barbarash O.L. Treatment for dyslipidemia in comorbid patients in real clinical practice: potentialities of pitavastatin. Russian Medical Inquiry. 2021;5(4):218–224 (in Russ.). DOI: 10.32364/2587-6821- 2021-5-4-218-224.

COVID-19: ЧТО ПЕДИАТРЫ УЗНАЛИ ОБ ОСОБЕННОСТЯХ ИММУННОГО ОТВЕТА НА НОВУЮ КОРОНАВИРУСНУЮ ИНФЕКЦИЮ ЗА ГОД БОРЬБЫ С НЕЙ

A year ago, the world heard about an outbreak of a new severe coronavirus infection in China, which later, after its rapid spread across the globe, WHO defined as a pandemic. Pediatricians, of course, expected the worst-case scenario and mass illness of the most vulnerable patients – children and people of older age groups with a new infectious disease. From the immunological point of view, everything is obvious – the new pathogen is most dangerous for those who have not yet formed a defense against it, or for those with weakened defense. But it quickly became clear that, unlike, for example, a flu pandemic, there is an unexpected situation when adults, including elderly and senile patients, become seriously ill and die, and children remain practically outside the spread of the infectious process. During a year of living «in a new reality», not only physicians, but all of humanity learned to respond to a new infectious challenge, empirically looking for possible therapeutic or diagnostic interventions and at the same time trying to plan and implement scientific research that would help shed light on the questions posed. For the first time, the international medical community united to perform serious clinical trials of drugs that were proposed for the treatment or prevention of COVID-19. As a result of actions of scientists and clinicians around the world, answers to some questions were obtained, however, most of the information on the impact of the new coronavirus on the human body, including children, is still unavailable to medical practitioners. The review presents latest data on the causative agent of the new coronavirus infection, its effect on the body of children and adults, describes peculiarities of immune response to the new virus, and outlines basic principles of managing such patients in real clinical practice.

Thrombolytic Therapy in Normotensive Patients with Pulmonary Embolism (Data from the Retrospective Study)

Background. The thrombolytic therapy is absolutely recommended for patients in shock or hypotension because the benefits are clearly outweighing the risks. However, in hemodynamically stable patients, including those with acute right ventricular dysfunction and/or myocardial damage, thrombolysis has a significantly lower evidence level.Aim. To study the criteria based on which doctors decide to conduct thrombolytic therapy in normotensive patients in real clinical practice according to the retrospective data.Material and methods. A single-center retrospective cohort study analyzed medical records of patients hospitalized in 2006-2017 with a verified diagnosis of pulmonary embolism (PE) and who had a systolic blood pressure >90 mm Hg at the time of admission.Results. The present study population included 299 patients with a verified diagnosis of PE from 2006 to 2017 years. Patients were divided into two groups: with thrombolysis (group 1) and without thrombolysis (group 2). Logistic regression analysis showed that age younger than 60 years, the presence of varicose veins of the lower extremities, skin cyanosis, syncope in the debut of PE were independent clinical factors that significantly influence the doctor's decision to perform thrombolysis. Increased troponin I, right ventricular dysfunction, and the severity of PE according to the PESI score showed no significant impact on this decision. In-hospital mortality in the group 2 was 1.9% (5 patients), while there were no deaths in the group 1. But the analysis of the association of thrombolysis with survival was difficult to perform due to the low incidence of deaths and the small number of patients in the group with thrombolysis (odds ratio 0.34; 95% confidence interval 0.03-8.18; р=0.856). No major bleeding was registered in any group.Conclusion. We were not able to clearly identify independent clinical or instrumental factors that influence the decision to perform thrombolysis in patients with PE outside the framework of evidence-based medicine. Further research is needed.

Ustekinumab in Crohn's disease: Effectiveness and safety in clinical practice

Abstract Introduction Ustekinumab (UST) is a monoclonal antibody against IL-12/23 approved in Spain (2017) to treat moderate/severe Crohn's disease. Objective To evaluate the effectiveness and safety in real clinical practice in patients treated with UST in our centre. Methods This is a prospective observational study including patients who started UST from 08/01/2017 to 02/28/2019 with follow-up up to that date. We analyse response and remission in weeks 16, 24 and 52, using “Crohn's Disease Activity Index” (response if 100 point decrease and remission if Results We included 61 patients with a median duration of Crohn's disease of 14.6 years (0–36). The 83.6% of patients without steroids and 73.8% without associated immunosuppressors. Previously all patients had received anti-TNF and 14.8%, in addition, vedolizumab. We observed a good correlation between Crohn's Disease Activity Index and Physician's Global Assessment (r = 0.89, p Conclusion UST is an effective and safe treatment in real clinical practice with high rates of clinical remission at week 16, 24 and 52 regardless of the order of biological used and the reason for starting UST.

Impact of Comorbidities on Disease Activity, Patient Global Assessment, and Function in Psoriatic Arthritis: A Cross-Sectional Study.

IntroductionThe aim of this study was to evaluate the impact of comorbidities on disease activity, patient’s impact of the disease, patient global assessment, and function in psoriatic arthritis (PsA).MethodsConsecutive PsA patients were enrolled in this cross-sectional study. During the visit, the patients underwent a complete physical examination and clinical/laboratory data were collected, including type and number of comorbidities, recorded as simple comorbidity count (SCC).Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and the Minimal Disease Activity (MDA) was also evaluated. The Psoriatic Arthritis Impact of Disease (PsAID), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Patient Global Assessment of disease activity (PtGA) were also collected.ResultsA total of 144 patients were enrolled. At least one comorbidity was registered in 104 (72.2%) patients. The SCC was associated with DAPSA (β = 1.48, p = 0.013), PsAID (β = 0.41, p < 0.01), HAQ-DI (β = 0.11, p < 0.01) and PtGA (β = 0.50, p < 0.01). The comorbidities that showed an impact on outcome measures were anxiety and fibromyalgia (FM). Anxiety showed an impact on DAPSA (β = 14.46, p < 0.001), PsAID (β = 1.98, p = 0.039) and HAQ-DI (β = 0.54, p = 0.036). FM showed an impact on DAPSA (β = 6.46, p = 0.025), PsAID (β = 2.88, p < 0.001), HAQ-DI (β = 0.70, p < 0.001), PtGA (β = 2.00, p = 0.014), and MDA (β = − 2.79, p = 0.01). The median PtGA value was different among patients with different numbers of comorbidities.ConclusionsThis study showed that comorbidities, either as a simple comorbidity count number or as single comorbidity, might have an impact on the main domains affecting PsA patients in real clinical practice.

Ustekinumab en enfermedad de Crohn: efectividad y seguridad en práctica clínica

IntroductionUstekinumab (UST) is a monoclonal antibody against IL-12/23 approved in Spain (2017) to treat moderate / severe Crohn's disease. ObjectiveTo evaluate the effectiveness and safety in real clinical practice in patients treated with UST in our center. MethodsThis is a prospective observational study including patients who started UST from 08/01/2017 to 02/28/2019 with follow-up up to that date. We analyze response and remission in weeks 16, 24 and 52, using “Crohn's Disease Activity Index” (response if 100 point decrease and remission if <150) and Physician's Global Assessment. ResultsWe included 61 patients with a median duration of Crohn's disease of 14,6 years (0-36). The 83,6% of patients without steroids and 73,8% without associated immunosuppressors. Previously all patients had received anti-TNF and 14,8%, in addition, vedolizumab.We observed a good correlation between Crohn's Disease Activity Index and Physician's Global Assessment (r = 0,89, p <.001). In week 16 (n = 45) 75,6% response (57,8% remission), in week 24 (n = 35) 69,9% response (45,7% remission) and in week 52 (n = 12) 75% response (58.3% remission). There were no statistically significant differences in the response/remission rates at week 16 or 24 depending on the reason for the onset of UST or the number of previous biologics. In 2 patients it was withdrawn due to toxicity (arthralgia / myalgia). ConclusionUST is an effective and safe treatment in real clinical practice with high rates of clinical remission at week 16, 24 and 52 regardless of the order of biological used and the reason for starting UST.

Effectiveness of netakimab in real clinical practice in patients with severe forms of psoriasis

Psoriasis refers to genetically deterministic chronic inflammatory dermatoses, which are characterized by systemic immuno-mediated inflammatory response with preferential activation of the IL -23/-17 axis, growth deviation and keratinocyte differentiation.Material and methods. There were 21 patients under supervision with moderate to severe plaque psoriasis. Nine (42.8 %) patients did not receive previous systemic therapy; 3 (14.2 %) patients received apremilast at a dose of 30 mg twice a day during a year, 4 (19.0 %) patients were prescribed methotrexate at a dose of 15 mg subcutaneously weekly, for at least a year; 5 (23.8 %) patients received secukinumab at 300 mg subcutaneously once every 4 weeks for a year. All patients had a lost of effect or had developed side effects, which determined a change in therapeutic tactics.Results. Among the patients who were earlier not receiving treatment treatment after therapy with netakimab was started, the PASI index made 3.5 ± 1.1 (decrease by 94.4 %), the PASI index at the patients who were earlier receiving sekukinumab was 4.5 ± 1.1 (decrease by 81.9 %), among the patients who were earlier receiving the methotrexate the PASI index was 8.5 ± 1.3 (decrease by 89.9 %), at the patients who were earlier receiving apremilast the PASI index was 9.5 ± 2.1 (decrease by 86.3 %).Conclusions. Improvement in skin symptoms was accompanied by improvement of patients’ quality of life. Thus, the DLQI decreased by 77.9 % in the group of patients who had not previously received systemic therapy, by 77.4 % and 76.4 % in patients who had previously received sekukinumab and methotrexate therapy, respectively, and by 85.2 % in the group of patients who had previously received apremilast.

The Effects of Telmisartan and Its Combinations on Office Blood Pressure: Results of Prospective Observational Study TAINA

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.Results. Significant (p&lt;0.001 in all cases) change in office BP compared with the initial data were recorded in all study groups of therapy already at 4 weeks of treatment and became even more pronounced at 12 weeks. In the telmisartan monotherapy group, BP decreased from 155.7±10.7/92.2±7.6 mm Hg to 131.4±12.1/80.8±7.3 mm Hg at the end of the 4th week and to 125.3±7.6/78.2±6.1 mm Hg – at the end of the 12th week. Similarly, after treatment with the combination of telmisartan and hydrochlorothiazide, BP decreased from 162.7±12.6/94.3±7.9 mm Hg to 133.2±12.5/81.6±8.4 mmHg at the end of the 4th week and to 126.0±7.8/78.4±6.7 mm Hg – at the end of the 12th week. In telmisartan/amlodipine group, a decrease in BP also occurred, from 162.5±13.2/94.6±8.6 mm Hg to 132.8±14.5/81.3±7.5 mm Hg on the 4th week and to 125.4±8.7/78.4±5.6 mm Hg at the end of follow up (12 weeks). The proportion of patients who reached the target BP (&lt;140/90 mm Hg) after treatment with telmisartan as monotherapy was 91.7%, after treatment with telmisartan+hydrochlorothiazide – 89.6%, after treatment with telmisartan+amlodipine – 92.8%. Throughout the program, prescribed therapy was well tolerated by patients. During the study, 47 adverse events (AEs) were recorded in 36 patients: 31 AEs with telmisartan monotherapy, 5 AEs with telmisartan/hydrochlorothiazide combination, and 11 AEs with telmisartan/amlodipine combination. Most of the AEs registered during the trial resolved by the end of the study, in four cases the date of AEs resolve is unknown, in two cases, at the time of completion of the study, AEs continued.Conclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined.

Control Of Anticoagulation Therapy in Atrial Fibrillation (COAT-AF Study) in Real Clinical Practice

Aim. To study the frequency of prescribing anticoagulant therapy in outpatients with AF in accordance with clinical guidelines.Material and methods. Control Of Anticoagulation Therapy in Atrial Fibrillation (COAT-AF) observational study was conducted at the Saint Joasaph Belgorod Regional Clinical Hospital from January 1, 2016 to December 31, 2017. Patients with AF represented 15.5% of all patients admitted to cardiology department N1. 429 patients were included into the study: 203 women, 226 men; aged of 62.55±11.12 years. Exclusion criteria were mitral stenosis, mechanic prosthetic valve, first episode of AF. CHA2DS2-VASc score was used in all patients for calculation the risk of ischemic stroke and systemic thromboembolism. For patients that were treated by warfarin international normalization ratio (INR) was assessed at admission and discharge from the hospital.Results. From 429 patients 35 had 1 point according to the CHA2DS2-VASc scale, 393 (91.6%) patients had ≥2 points. Only 1 patient had 0 point. Therefore, most patients had absolute indications to anticoagulant therapy. At admission 60 (14%) patients received new oral anticoagulants (NOACs), 213 (49.6%) – warfarin, 156 (36.4%) – did not take any oral anticoagulant. Among patients receiving warfarin only 36 (8.4%) had target INR at admission. Therefore, effective anticoagulant therapy was observed only in 22.4% of patients in real clinical practice. Analyzing anticoagulant therapy in 2016 and 2017 we found a significant increase in NOAC prescription from 10.4% in 2016 to 18.9% in 2017 (p=0.0193).Conclusion. Our data reflects important gaps of anticoagulant therapy in real clinical practice. We compare our results with other Russian registries that included AF-patients. Data at admission and discharge suggests that there are great possibilities for optimization of anticoagulant therapy mainly with NOACs.

Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice

96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated). After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months 62.5%, endoscopic remission 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%). Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

Adherence to Treatment with New Oral Anticoagulants in Atrial Fibrillation Patients in Real Clinical Practice (Results of the ANTEY Study)

Aim. To study adherence to treatment with new oral anticoagulants (NOAC) and factors associated with it in patients with non-valvular atrial fibrillation (AF) within the outpatient PROFILE registry.Material and methods. ANTEY study included 201 patients with AF from the PROFILE registry (89.3%): 118 males (58.7%) and 83 females (41.3%), aged 71.1Ѓ}8.7 years. The study consisted of two visits half a year apart (V0, V1) and a phone contact (PC) one year after V0. During V0 all patients were recommended to start therapy with one of the NOACs. Adherence to therapy was assessed during all visits with the use of the original questionnaire – National society of evidence-based pharmacotherapy (NSEPh) adherence scale, 8-item Morisky Medical Adherence Scale (MMAS-8) and direct doctors’ questioning.Results. During V0 111 (55.2%) patients were recommended the use of rivaroxaban; 47 (23.4%) – the use of dabigatran and 43 (21.4%) – the use of apixaban. During V1 based on the results of the NSEPh adherence scale 155 (77.5%) patients were completely adherent (strictly followed doctors’ recommendations), 5 patients were partially adherent (violated doctors’ recommendations), 7 patients were partially non-adherent (stopped taking NOACs), and 33 patients were completely non-adherent (did not start taking NOACs). Out of 197 patients who completed MMAS-8 questionnaire 157 (79.7%) patients were partially adherent to treatment and 40 (20.3%) patients were non-adherent. None of the patients were completely adherent to treatment. According to doctors’ questioning, by the time of the PC 15 patients had not started taking the recommended NOAC – were completely non-adherent (CNA). According to the NSEPh adherence scale, by the time of the PC out of 197 patients (4 patients died) 158 patients were completely adherent to treatment, 6 – partially adherent, 18 – partially non-adherent and 15 – CNA. According to MMAS-8, by the time of the PC 153 (77.7%) patients were partially adherent to treatment, and 44 (22.3%) patients – non-adherent (none of the patients were completely adherent). Out of 15 CNA patients MMAS-8 revealed only 4 (27,6%) during B1, and 6 (40%) during the PC. NSEPh adherence scale revealed all CNA patients. The main reason for refusing to start NOAC therapy was their high price. Recently started use of NOACs was stopped mostly due to adverse effects of therapy (bleeding). The most common factors increasing patients’ adherence to NOACs were previous experience of taking this group of drugs and no history of any adverse effects during therapy.Conclusion. The ANTEY study showed relatively high adherence to NOACs prescribed by doctors of the specialized cardiology department of the scientific center. The most common factors associated with early non-adherence to the new drug were high price and adverse effects of therapy, the latter influenced prolonged adherence as well. Previous experience of taking this group of drugs and no history of any adverse effects during therapy increased adherence to NOACs.

Efficacy of micronized purified flavonoid fraction in treatment of chronic venous oedema

The purpose of the study was to assess efficacy and safety of using in real clinical practice micronized purified flavonoid fraction (Detralex) in patients with chronic venous oedema. The study enrolled a total of 708 patients presenting with chronic venous disease, belonging to C3EpAsPr according to the CEAP classification (chronic venous oedema), who. depending on the accepted clinical practice by expert physicians were prescribed compression and phlebotropic therapy, as well as undergoing surgical interventions. The main criteria for efficacy of the micronized purified flavonoid fraction included the dynamics of chronic venous oedema, vein-specific symptoms, as well as the main parameters of quality of life. Assessment was made using visual analogue scales, the vein-specific questionnaire CIVIQ-14, and the method of discs for measuring the volume of the crus. The obtained findings demonstrated significant positive dynamics of the main vein-specific symptoms assessed by a visual analogue scale. When comparing between the visits of recruitment into the study and its termination the feeling of heaviness in calves decreased form 5.38±2.19 cm to 1.56±1.56 cm (p<0.001), pain in the calf diminished from 4.24±3.39 cm to 1.12±1.37 cm (p<0.001), feeling of oedema dropped from 5.68±2.44 cm to 1.38±1.59 cm (p<0.001), severity of nocturnal cramps fell from 2.46±2.30 cm to 0.43±1.01 cm (p<0.001), and intensity of skin inching from 1.46±2.06 cm to 0.43±1.01 cm (p<0.001). Positive dynamics of venous-specific symptoms appeared to be accompanied by significant improvement of all dimensions of quality of life according to the CIVIQ-14 scale: by the pain scale from 41.0±19.1% to 12.8±11.6% (p<0.001), by the physical condition scale - from 31.6±23.8% to 11.1±15.4% (p<0.001), by the psychological state scale - from 24.5±21.1% to 5.7±9.0% (p<0.001). The global index of quality of life also improved significantly from 32.4±18.5% to 9.9±9.9% (p<0.001). The results of the intervention along all the examined parameters (external appearance, possibility of wearing various clothes and increasing the quality of the self-performed work, to improve both interactions with surrounding people and the social activity and rest) turned out better than expectations form an intervention. The volume of the crus as the main criterion over the period of follow up averagely by the group decreased from 3.07±0.84 to 2.78±0.80 litres (p<0.001). A significant decrease in the calf volume from 3.03±0.87 to 2.77±0.85 litres was observed in 288 patients who during the follow up period were not subjected to surgical interventions, with no significant differences in the dynamics of chronic venous oedema revealed between the operated patients and those having received conservative treatment alone. According to a meta-analysis, the micronized purified flavonoid fraction (Detralex) turned out to possess better parameters in relation to therapy of chronic venous oedema as compared with other phlebotropic agents. Therefore, it appears absolutely logical to predominantly use the micronized purified flavonoid fraction in real clinical practice in patients with the CEAP C3 clinical class, which was registered in our study. An important result was also the fact that within the specified terms of follow up surgical intervention demonstrated no significant advantage over conservative therapy alone in treatment of chronic venous oedema. Moreover, conservative treatment in the form of a combination of compression and phlebotropic therapy demonstrated a dynamic decrease in the volume of the affected extremity with a probable transition of the CEAP C3 clinical class to C2. The micronized purified flavonoid fraction (Detralex) at a standard daily dose of 1000 mg in a combination with compression therapy irrespective of the surgical intervention performed resulted in a significant dynamic decrease in the volume of the calf in patients with chronic diseases of lower limb veins (C3EpAsPr according to the CEAP classification). An anti-oedematous effect of the micronized purified flavonoid fraction (Detralex) in a combination with compression manifests itself during the entire period of treatment.

Survival outcomes in stage IV small-cell lung cancer (IV-SCLC): Analysis from SEER database

Abstract Background SCLC represents the subtype with worst survival among lung cancer patients. Despite initial good response to platinum based chemotherapy in extensive disease, these patients relapse fast with an unfortunate prognosis. The majority of overall survival (OS) data reported show a median between 8-10 months (mo) based on randomized clinical trials and meta-analysis. Methods The aim of this study is to analyze survival outcomes in IV-SCLC patients in real clinical practice based on SEER database and identify which patients have worse outcomes. We selected all patients with SCLC from SEER database diagnosed between 2010-2015. Bivariate analysis was used by chi-square determination for the association of binary qualitative variables and the ANOVA test to compare 2 or more variables. A multivariate analysis using Cox regression was performed, measuring the effect by Hazard Ratios (HR) and their 95% confidence intervals to determine the impact of these prognostic factors on OS. AJCC 7 was used for TNM staging. Results We included 26,221 patients with SCLC. Men: 50.7%. 55.7% patients were ≥ 65 years old. Median age: 67 years old. 82% were caucasian. 70.84% were stage IV. These patients showed a median OS (mOS) of 6mo (5.83-6.17). 45.37% of them had liver metastasis (mets), bone: 33.41%, brain: 23.86%, lung: 19.47% and other mets sites: 16.88%. Median OS in patients with liver mets, bone, brain and lung were 4 (3.79-4.21), 6 (5.74-6.26), 6 (5.71-6.29) and 5 mo (4.63-5.37) respectively. Patients involving both lung and liver mets with 3 or more mets sites showed the worst survival with 3 (1.99-4.00) and 4 (3.11-4.89) mo of mOS respectively. The percentage of patients alive at 6, 12, 24 y 60 mo were 47.70%, 21.64%, 5.91% and 1.61% respectively. Conclusion This real world data analysis reflects that the chance of having long term survivors in SCLC is very low and that mOS has not been improved over the last years. The introduction of new therapies such as immune checkpoints opens a new opportunity for long term survival and better outcomes in this aggressive disease. Legal entity responsible for the study Roche Farma S.A. Funding Roche Farma S.A. Disclosure J. de Castro Carpeno: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Tesaro. M. Cobo Dols: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer. M. Domine Gomez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer. P. Ruiz Gracia: Full / Part-time employment: Roche. L. Crama: Full / Part-time employment: Roche. M.R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer.

Contemporary epidemiology and treatment of hospitalized heart failure patients in real clinical practice in China

Objective: To observe the etiology, comorbidities, clinical features and treatment patterns of hospitalized patients with heart failure (HF) in China. Methods: Data were collected prospectively on hospitalized patients with HF who were enrolled in China Heart Failure Center Registry Study from 169 participating hospitals from January 2017 to August 2018. In this cross-sectional study, patients were stratified by left ventricular ejection fraction (LVEF) category: heart failure with reduced ejection fraction (HFrEF, LVEF<40%); heart failure with mid-ranged ejection fraction (HFmrEF, 40%≤LVEF<50%) and heart failure with preserved ejection fraction (HFpEF, LVEF≥50%). The clinical data were collected, including demographic information, diagnosis, signs, electrocardiogram, echocardiography, laboratory tests, and treatment. Results: A total of 31 356 hospitalized patients with HF were included, 19 072 (60.8%) were males and the average age was (67.9±13.6) years old. The common causes of HF were hypertension (57.2%), coronary heart disease (54.6%), dilated cardiomyopathy (14.7%), valvular heart disease (9.2%). The common complications were atrial fibrillation/atrial flutter (34.1%), diabetes (29.2%), and anemia (26.7%). 32.8% of patients had a history of hospitalization for HF within the previous 12 months. There were 11 034 (35.2%) patients with HFrEF, 6 825 (21.8%) patients with HFmrEF and 13 497 (43.0%) patients with HFpEF. Compared with patients with HFpEF, patients with HFrEF had a lower systolic blood pressure ((124.7±21.1)mmHg(1 mmHg=0.133 kPa) vs. (134.9±22.9)mmHg), faster heart rate ((85±19) beats/minutes vs. (81±19)beats/minutes), and higher percentage of New York Heart Association (NYHA) class Ⅳ, smoking, alcohol, left bundle branch block, and QRS time≥130 ms, and higher levels of blood uric acid, BNP, and NT-proBNP (all P<0.05). Compared with patients with HFmrEF and HFrEF, patients with HFpEF were older, more women, and higher comorbidity burden including hypertension, atrial fibrillation/atrial flutter, anemia and chronic obstructive pulmonary disease (all P<0.05). HFmrEF took a mid-position between HFrEF and HFpEF in age, gender, heart rate, systolic blood pressure, hypertension, atrial fibrillation/atrial flutter, anemia, and chronic obstructive pulmonary disease (all P<0.05). Patients with HFmrEF had the highest proportion of coronary heart disease, myocardial infarction and percutaneous coronary intervention (all P<0.05). During hospitalization, loop diuretics were used in 90.2% of patients, and intravenous inotropics were used in 20.4% of patients. The use of ACEI/ARB/ARNI, β blockers and aldosterone receptor antagonists at discharge were 71.8%, 79.1% and 83.6% in HFrEF and 69.9%, 75.5% and 72.4% in HFmrEF, respectively. The use of digoxin at discharge was 25.3% (HFrEF 36.7%, HFmrEF 23.1%, HFpEF 17.0%). The rates of cardiac resynchronization therapy and implantable cardioverter defibrillator in HFrEF were 2.7% and 2.1%. Conclusions: Among the hospitalized patients with HF in China, coronary heart disease and hypertension are the mostly prevalent causes. HFpEF accounts for a large proportion of hospitalized patients with HF. HFrEF, HFmrEF and HFpEF have different etiology and clinical features. In real-world, there are still large gaps in the effective application of the guideline recommended therapies to HF patients, especially the non-pharmacological therapy option, which needs to be improved further in China.

PIN3 SOFOSBUVIR/VELPATASVIR VS GLECAPREVIR/PIBRENTASVIR IN GENOTYPE 3 HEPATITIS C VIRUS INFECTED PATIENTS

Genotype 3 (G3) is the second most prevalent hepatitis C virus (HCV) genotype in Europe, and causes a faster progression to liver cirrhosis. Sofosbuvir/Velpatasvir (SOF/VEL) or Glecaprevir/Pibrentasvir (GLE/PIB) are the recommended therapies for most G3-HCV patients. The objective of this study is to analyze the effectiveness and safety of 8-24 weeks treatment regimens of SOF/VEL vs GLE/PIB in a cohort of G3-HCV infected patients in real clinical practice. Prospective, observational, comparative study in G3-HCV infected patients, who initiated treatment with SOF/VEL or GLE/PIB during 2017 and 2018. Exclusion criteria: patients from penitentiary centers and pediatrics. Effectiveness main variable: sustained virological response 12 weeks post-treatment (SVR12). Safety variable: treatment withdrawal secondary to severe adverse events (AE). Covariates: gender, age, HIV co-infection, previous treatment, liver transplantation, cirrhosis, fibrosis, and previous antiviral treatment. Statistical method: intention-to-treat analysis; statistical signification calculated with Fisher exact or Mann-Whitney tests. Study authorized by the Health System Investigation Committee. 76 patients included, 46 treated with SOF/VEL±RBV and 30 with GLE/PIB. No basal differences between groups observed related with age, gender, HIV co-infection, fibrosis stage, cirrhosis and previous antiviral treatment (p>0.1). 95.7% treated with SOF/VEL±RBV vs 96.7% treated with GLE/PIB reached SVR12 (p=0.7). 83.3% cirrhotic vs 98.4% non-cirrhotic patients reached SVR12 (0.09). 100% patients with low fibrosis (F0-2) compared to 85.7% patients with advanced fibrosis (F3-4) reached SVR12 (p=0.03). SVR12 in treatment-naïve vs treatment-experienced was 95.7% vs 100.0% respectively (p=0.57), without statistically significant differences independent of the treatment group (p=0.28 for SOF/VEL±RBV; p=0.18 for GLE/PIB). Any degree AEs rate was 21.1% (11.3%-30.9%, 95%CI); no patient presented serious AE, so none of the patients in both cohorts required antiviral treatment withdrawal. SOF/VEL or GLE/PIB are highly effective and safe for G3-HCV infected patients, with a lower effectiveness in patients with advanced fibrosis F3-4.