Clinical Efficacy and Tolerability of Antihypertensive Therapy with Single Pill Combinations of Telmisartan in Patients with Arterial Hypertension in Clinical Practice According to the ON TIME Observational Study

Aim. To assess the clinical outcomes and tolerability of antihypertensive therapy with single pill combinations (SPC) amlodipine + telmisartan and hydrochlorothiazide + telmisartan in clinical practice.Material and methods. Patients with hypertension of grade 1-3 (n=13647; 57.6% women; age 59.3±11.4 years) who received therapy with SPC amlodipine + telmisartan or hydrochlorothiazide + telmisartan were included in an observational multicenter study. Information on complaints, history, previous therapy, history of novel coronavirus infection (COVID-19) during the previous year was obtained. Also, measurement of height, body weight, waist circumference (WC) and hips (HC), office blood pressure (BP) three times with an interval of 4 weeks, completion of questionnaires of satisfaction with therapy using the Likert scale, and assessement of adherence to therapy according to the patient's opinion was performed.Results. A statistically significant decrease in systolic (SBP) and diastolic blood pressure (DBP) was found both in all patients and in the analysis of subgroups according to the grade of hypertension (p<0.001 between visits in all cases). The degree of BP reduction depended on baseline BP levels. The average decrease in SBP/DBP at the 3rd visit for the grade 1 hypertension was 24.5/14.6 mm Hg, for the grade 2 hypertension – 34.4/16.8 mmHg, for the grade 3 hypertension – 49.6/22.1 mmHg (p<0.001 between groups). Target levels of SBP (≤140 mmHg) and DBP (≤90 mmHg) were achieved in 95.3% and 98.1% of patients, respectively. Target levels of SBP (≤130 mmHg) and DBP (≤80 mmHg) were achieved in 74.9% and 78.2% of patients, respectively. WC decreased by 0.5%; HC – by 1.5%; body weight – by 0.42% (p<0.001 in all cases). Scores in patients with a history of COVID-19 did not differ from those in individuals without a history of COVID-19. There were no violations of the therapy regimen during the observation period in 94% of patients. Most doctors and patients were "satisfied" or "completely satisfied" with the clinical effect, convenience and tolerability of therapy. Adverse events occurred in 1.35% of patients.Conclusion. Therapy with SPC amlodipine + telmisartan or hydrochlorothiazide + telmisartan in clinical practice had a high antihypertensive efficacy and had an optimal safety profile. The efficacy of therapy did not depend on the initial grade of hypertension, as well as the past infection with COVID19. The results of the ON TIME study confirm the feasibility of using the SPC amlodipine + telmisartan and hydrochlorothiazide + telmisartan for a wide range of hypertensive patients

Nucleon Resonances and Quark Structure

A pedagogical review of the past 50 years of study of resonances, leading to our understanding of the quark content of baryons and mesons. The level of this review is intended for undergraduates or first-year graduate students. Topics covered include: the quark structure of the proton as revealed through deep inelastic scattering; structure functions and what they reveal about proton structure; and prospects for further studies with new and upgraded facilities, particularly a proposed electron-ion collider.Comment: 21 pages, 15 figure

Patient adherence after coronary bypass grafting: different facets of same matter. A systematic review

Background. Adherence in cardiological patients is a leading challenge due to a high society burden imposed by cardiovascular diseases (CVDs) through morbidity, reduced life expectancy, disability and high mortality rates in population. Despite the availability of highly effective medicines and high-technology care, the success of CVD treatment remains insufficient. A particular focus should be placed on patients with previous coronary artery bypass grafting (CABG).Objectives. A review of reasoning for non-adherence to medication and non-medication management in post-CABG patients and current methods influencing it.Methods. Russian-language and foreign literature was mined in the eLibrary and PubMed databases with the query keywords “medication adherence” [приверженность терапии], “coronary artery disease” [ишемическая болезнь сердца], “coronary artery bypass surgery” [коронарное шунтирование], “coronary revascularisation” [вторичная профилактика после коронарного шунтирования]. The review included papers published within 2016–2020, as well as selected relevant publications from 2003–2015, to cover 52 sources irrespective of study design and language. Content and descriptive analyses were used as research tools.Results. Coronary heart disease (CHD) poses an important health, social and economic problem worldwide as a leading cause of reduced life expectancy, disability and high mortality. Non-compliance with medication significantly bursts medical expenditures [1]. Coronary artery bypass grafting is used widely to treat multivessel coronary lesions both in stable and acute CHD. Secondary preventive techniques successfully preclude adverse post-CABG events, but adherence to post-CABG treatment is often low. The non-adherence rationale rarely links to a single factor but is rather complex and multifaceted. It includes social and economic reasons, systemic health care or personnel, therapy and patient-related factors. Methods are developing and refining to improve adherence to both non-medication and medication interventions.Conclusion. Clinical trials to improve secondary prevention adherence in patients after coronary artery bypass grafting will allow a wider implementation of relevant methods in outpatient management of this patient category

Dijet production as a centrality trigger for p-p collisions at CERN LHC

We demonstrate that a trigger on hard dijet production at small rapidities allows to establish a quantitative distinction between central and peripheral collisions in pbar-p and p-p collisions at Tevatron and LHC energies. Such a trigger strongly reduces the effective impact parameters as compared to minimum bias events. This happens because the transverse spatial distribution of hard partons (x >~ 10^{-2}) in the proton is considerably narrower than that of soft partons, whose collisions dominate the total cross section. In the central collisions selected by the trigger, most of the partons with x >~ 10^{-2} interact with a gluon field whose strength rapidly increases with energy. At LHC (and to some extent already at Tevatron) energies the strength of this interaction approaches the unitarity ('black-body') limit. This leads to specific modifications of the final state, such as a higher probability of multijet events at small rapidities, a strong increase of the transverse momenta and depletion of the longitudinal momenta at large rapidities, and the appearance of long-range correlations in rapidity between the forward/backward fragmentation regions. The same pattern is expected for events with production of new heavy particles (Higgs, SUSY). Studies of these phenomena would be feasible with the CMS-TOTEM detector setup, and would have considerable impact on the exploration of the physics of strong gluon fields in QCD, as well as the search for new particles at LHC.Comment: 17 pages, Revtex 4, 14 EPS figures. Expanded discussion of some points, added 3 new figures and new references. Included comment on connection with cosmic ray physics near the GZK cutoff. To appear in Phys Rev

Potential of valsartan+sacubitril therapy in hypertensive heart disease

The course of hypertension is often complicated by left ventricular hypertrophy (or hypertensive heart disease, HHD). The main “corridor” of natural HHD is development of heart failure with preserved ejection fraction (HFpEF). With HFpEF, the bioavailability of natriuretic peptides (NP) is significantly reduced, as a result of which the activity of cGMP-PKG signaling pathway, which plays a key role in maintaining normal diastolic function, weakens. It is possible to increase the activity of this pathway using the neprilysin inhibitor sacubitril. In case of HFpEF, the greatest efficacy from valsartan+sacubitril therapy should be expected in patients with severe concentric LVH, who have the most pronounced natriuretic peptide deficiency. Valsartan+sacubitril therapy has a clear hypotensive effect, causes a reversal of left ventricular hypertrophy and fibrosis. Since no effective treatment has yet been found for HFpEF, the main way for HHD treatment should be to prevent the diastolic dysfunction progression, which justifies valsartan+sacubitril therapy starting from the early/ asymptomatic stages

The influence of Losartanum and Amlodipinum fixed combination use on cardiovascular complications risk factors seasonal variability in patients with arterial hypertension

Rationale: The influence of drugs on adaptation to high temperatures and seasonal variability of cardiovascular disease factors is one of the most important issues of treatment raised during re-cent heat waves. The safety of calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) use during heat waves is quite controversial. Aim: To assess the seasonal variability of hemodynamic parameters, vessel wall stiffness, lipid, carbohydrate and electrolyte metabolism in patients with arterial hypertension (AH) and to as-sess safety and effectiveness of fixed combination of Losartanum and Amlodipinum (Lortenza® KRKA) use according to one-year follow-up results. Materials and methods. The study included 26 patients with stage 1 and 2 AH aged from 42 to 81 years. Office blood pressure measurement, electrocardiography, volumetric sphygmography (pulse-wave velocity, cardio-ankle vascular index), serum chemistry, blood osmolarity tests were performed. Visual Analog Scale (VAS), Heat Questionnaries and self-control diaries were also assessed. The baseline visit took place in spring of 2016, the first visit - in May-June 2016, the second - during the heat wave, the third - in September-October 2016, the fourth - in January-February 2017, and the fifth - in April-May 2017. Results. The treatment resulted in systolic and diastolic blood pressure decrease (р=0.000) to target value which persisted during the follow-up period. According to the self-control diaries 81% of patients did really control BP. During the heat wave only 58% of patients succeeded in BP control, in autumn - 63%, in winter and spring - 81% and 86%, respectively. By the third visit the heart rate decreased on -6.0 (-11.1; -2.8) beats per minute, p=0.007. The decrease in pulse-wave velocity from 15.2±3.4 m/s to 13.6±2.7 m/s, p=0.01 and CAVI on -2.1 (-2.9; -0.65), p=0.01 was observed on the third visit. Decrease in uric acid level (

Improving outpatient care in chronic heart failure

Despite advances in pharma and high-technology medicine, the rate of burdensome hospital admissions and mortality in patients with chronic heart failure (CHF) remains high. Over half of all admission-entailing decompensations have been repeatedly shown to emerge from non-compliance with outpatient prescriptions. Poor adherence to medication and non-medication treatment can only be broken by improving the patient’s awareness of the disease and his closer monitoring by healthcare professionals. The power of clinical and laboratory illness monitoring in line with the recommended quality criteria of medical aid in heart failure (HF) is strongly limited today by time resources available in outpatient and midwifery clinics. Meanwhile, an international and certain domestic experience has been built up to run CHF outpatient centres with involvement of specially-trained nursing and senior medical staff. Analytic evidence on such centres suggests a reduction in mortality and hospitalisation rate among the visiting patients. To combat existing drawbacks of CHF outpatient care, the National Medical Research Center of Cardiology in alliance with the Specialist Society of Heart Failure have developed the nurses’ guidelines for CHF rooms and are launching a medical staff training programme to manage CHF rooms, registry and data analysis. Furthermore, a procedure has been developed for patient routing to regional CHF outpatient cabinets that is being actively deployed in the Tyumen Region

Prognostic value of subclinical atherosclerosis in patients with a SCORE risk <5%: data from a 10-year follow-up

Aim. To evaluate the contribution of subclinical atherosclerosis to the stratification of patients with a SCORE risk of cardiovascular events (CVEs) &lt;5% based on a 10-year follow-up.Material and methods. The study included 379 patients with SCORE risk of CVEs &lt;5% (82 men, 297 women). In 2009, all patients underwent clinical examination, carotid artery (CA) ultrasound with the detection of plaques, total CA occlusion, intima-media thickness (IMT) of the common carotid artery (CCA). The plaque number was determined as the total number of all plaques in 6 following segments: both CCAs, both CCA bifurcations and both internal carotid arteries. The total stenosis was calculated as the sum of stenoses in 6 CA segments in %. In 2019, a telephone survey of patients was conducted with a questionnaire assessing the following CVEs: all-cause death, cardiovascular death, myocardial infarction (MI), stroke, myocardial revascularization, cardiovascular hospitalizations, and composite endpoint.Results. The initial patients’ age ranged from 35 to 67 years (51,1±7,5 years). Plaques from 20% to 50% were detected in 303 participants (79,94%). Over the past 10 years, there have been 5 cardiovascular deaths (1,3%), 7 MIs (1,8%), 5 cases of unstable angina (1,3%), 12 cases of myocardial revascularization (3,2%), 15 strokes (4,0%), 51 cardiovascular hospitalizations (13,5%). The proportion of patients with registered endpoints (CVE+) was 22,4% (n=85). The groups of patients with and without CVEs differed in the level of systolic blood pressure (BP) and blood triglycerides, and did not differ in the level of diastolic BP, lipid profile, glucose, heart rate, smoking status, sex, and age. In the CVE+ group, there were higher values of CCA IMT (0,65 (0,64; 0,70) mm vs 0,62 (0,62; 0,66) mm, p&lt;0,05), total CA stenosis (102,5 (88,1; 120,8)% vs 80 (72,5; 88,1)%, p=0,01), and the CA plaque amount (4,0 (2,8; 3,9) vs 3,0 (2,6; 3,1), p=0,01), respectively. Total CA stenosis was an independent predictor of CVEs when adjusted for sex, age, systolic and diastolic BP (β=0,149; p&lt;0,05), but not for lipid profile. A ROC-analysis revealed a cut-off point for total CA stenosis of 82,5% (AUC=0,598, 95% confidence interval 0,5243-0,673, p&lt;0,05).Conclusion. The total CA stenosis has shown itself to be an independent predictor of CVEs in patients with a SCORE risk &lt;5%

Heavy Quark Photoproduction in Ultra-peripheral Heavy Ion Collisions

Heavy quarks are copiously produced in ultra-peripheral heavy ion collisions. In the strong electromagnetic fields, c c-bar and b b-bar are produced by photonuclear and two-photon interactions; hadroproduction can occur in grazing interactions. We present the total cross sections, quark transverse momentum and rapidity distributions, as well as the Q Q-bar invariant mass spectra from the three production channels. We consider AA and pA collisions at the Relativistic Heavy Ion Collider and Large Hadron Collider. We discuss techniques for separating the three processes and describe how the AA to pA production ratios might be measured accurately enough to study nuclear shadowing.Comment: Minor changes to satisfy referees and typo fixes; 52 pages including 17 figure

Azimuthal asymmetries of charged hadrons produced by high-energy muons scattered off longitudinally polarised deuterons

Azimuthal asymmetries in semi-inclusive production of positive (h^+) and negative hadrons (h^-) have been measured by scattering 160 GeV muons off longitudinally polarised deuterons at CERN. The asymmetries were decomposed in several terms according to their expected modulation in the azimuthal angle phi of the outgoing hadron. Each term receives contributions from one or several spin and transverse-momentum-dependent parton distribution and fragmentation functions. The amplitudes of all phi-modulation terms of the hadron asymmetries integrated over the kinematic variables are found to be consistent with zero within statistical errors, while the constant terms are nonzero and equal for h^+ and h^- within the statistical errors. The dependencies of the phi-modulated terms versus the Bjorken momentum fraction x, the hadron fractional momentum z, and the hadron transverse momentum p_h^T were studied. The x dependence of the constant terms for both positive and negative hadrons is in agreement with the longitudinal double-spin hadron asymmetries, measured in semi-inclusive deep-inelastic scattering. The x dependence of the sin phi-modulation term is less pronounced than that in the corresponding HERMES data. All other dependencies of the phi-modulation amplitudes are consistent with zero within the statistical errors.Comment: 12 pages, 11 Figures; revision 1 signs in Eq 5 corrected, polishe