On an analogue of Schwarz's reflection principle

We consider the Bergman space on the complex plane. We prove an analogue of Schwarz's reflection principle for unbounded quasidisks

Labor productivity impact of Internet infrastructure: evidence from a panel data

The study aims to shed more light on the relationship between Internet penetration and labor productivity by analyzing the aggregate cross-country panel data available for a wide range of countries in the period of 2001-2015. An overview of hypothetical mechanisms behind the communication technologies’ impact on productivity is provided, while the Augmented Solow model is used as a theoretic framework which motivates the choice of variables for empirical analysis. The estimates are obtained by using a selection of econometric estimators: fixed-effects OLS, mean-group common correlated effects and "Difference GMM" for additional robustness. Extensive empirical analysis is performed in order to account for certain well-known factors which can cause a bias in the estimates. When using a "penetration index" comprising a few dimensions of a country’s Internet development as a main variable of interest, the paper finds significant positive effect only in developed countries’ sample. Difference GMM estimates, however, are not significant. Additional analysis suggests that there may be a more pronounced connection between mobile subscriptions and labor productivity (and more than just in the developed countries). The independent variables’ estimates all have a theoretically expected signs. The results are fairly robust and allow a cautiously optimistic view on the relationship between Internet development and labor productivity growth. Nevertheless the extent of effect may sensitive to some unobserved country characteristic or industry

Atrial Fibrillation: a Marker or Risk Factor for Stroke

Atrial fibrillation (AF) is strongly associated with stroke risk, but an association by itself does not necessarily imply causation. The question remains whether AF is a risk factor for stroke and whether treatment that reduces the severity of AF will also reduce the burden of stroke. On the other hand, it is possible that AF is a risk marker associated with atrial insufficiency, in which structural and electrical atrial remodeling coexist, leading  to the clinical manifestations of AF and the risk of stroke simultaneously. Atrial fibrillation and stroke are inextricably linked to the classic Virchow pathophysiology, which explains thromboembolism as blood stasis in a fibrillating left atrium. This concept has been reinforced by the proven efficacy of oral anticoagulants for the prevention of stroke in AF. However, a number of observations showing that the presence of AF is neither necessary nor sufficient for stroke cast doubt on the causal role of AF in vascular brain injury. The growing recognition of the role of atrial cardiomyopathy and the atrial substrate in the development of stroke associated with AF, as well as stroke without AF, has led to a rethinking of the pathogenetic model of cardioembolic stroke. A number of recent studies have shown that AF is a direct cause of stroke. Studies in which cardiac implantable devices have been used to collect data on pre-stroke AF do not appear to show a direct time relationship. The presence of AF is neither necessary nor sufficient for stroke, which casts doubt on the causal role of AF in cerebrovascular injury. Known risk factors for stroke in the presence of AF are also recognized risk factors for ischemic stroke, regardless of the presence of AF. The risk of stroke in patients with AF in the absence of risk factors differs little from that in patients without AF. This work is devoted to an attempt to answer the question whether AF is a marker or a risk factor for ischemic stroke

Tocilizumab in rheumatoid arthritis: A case study of safety evaluations of a large postmarketing data set from multiple data sources

AbstractObjectivesTo evaluate the magnitude of serious adverse events (SAEs) observed in postmarketing reports of tocilizumab (TCZ) for rheumatoid arthritis (RA) in relation to SAEs observed in TCZ clinical trials and external epidemiology data.MethodsA total of 64,000 patient-years (PY) of TCZ exposure was needed to determine, with 90% power, whether rates of SAEs of interest (eg, death, hepatic, gastrointestinal, and cardiovascular) were ≥50% higher (agreed with the Food and Drug Administration) than expected. Reporting rates were calculated for spontaneously reported SAEs, open-label or unblinded postmarketing clinical trials (phase 3b/4), and a Japanese postmarketing surveillance program in the global postmarketing safety database. Event rates were calculated for the registrational placebo-controlled trials and long-term extension data. External comparators for anti-tumor necrosis factor (aTNF)-treated RA patients were derived from a US-based health care insurance claims database or published literature.ResultsThe global postmarketing safety database provided 65,099 PY of TCZ exposure; the aTNF external comparator population provided 53,360 PY. Spontaneous reporting rates per 100 PY (95% confidence interval) were 8.3 (8.1, 8.5) SAEs, 0.39 (0.34, 0.44) deaths, 0.06 (0.04, 0.08) serious hepatic events, 0.15 (0.12, 0.18) serious gastrointestinal events, 0.09 (0.07, 0.12) serious myocardial infarctions, 0.15 (0.12, 0.18) serious strokes, and 0.07 (0.05, 0.09) cardiac deaths in the global postmarketing safety database. These were of similar magnitude to corresponding rates from registrational clinical trials, the aTNF external comparator population, and published literature.ConclusionsSAE rates observed among postmarketing TCZ users were similar to those of various comparison populations. Predetermined design of studies to compare postmarketing AEs using multiple data sources is a useful strategy that can be applied to other medications

Left Ventricular Thrombosis: Current Perspective and Use of Direct Oral Anticoagulants

Left ventricular thrombus (LVT) is a serious risk factor for systemic embolism development. Despite the evident danger of this condition, current guidelines describe management of patients with this potentially fatal complication very briefly. LVT can complicate myocardial infarction where its incidence is around 10%, as well as various forms of cardiomyopathies and novel coronavirus infection. According to clinical guidelines vitamin K antagonists (VKAs) should be used as treatment of choice for thrombus resolution. However, experts point out that this therapy lacks necessary evidential base and bears certain difficulties because of pharmacokinetic and pharmacodynamical properties of VKAs. These drawbacks are absent in direct oral anticoagulants (DOACs), the possibility of using which in LVT is being actively studied. As for now, published results of 3 randomised clinical trials have demonstrated similar safety and efficacy profiles of DOACs and VKAs. Similarly, the majority of retrospective cohort studies did not observe significant differences between two groups, where some of them have shown superiority of DOACs especially in terms of earlier thrombus resolution. Nevertheless, some studies have found DOACs ineffective and even potentially unsafe regarding systemic embolism. Existing data does not allow to form an unambiguous conclusion about the equivalence of DOACs and VKAs for LVT resolution. Large randomised clinical trials are needed to determine efficacy and safety of such treatment in these patients

Patient perceptions of anticoagulant treatment with dabigatran or a vitamin K antagonist for stroke prevention in atrial fibrillation according to region and age : an exploratory analysis from the RE-SONANCE study

Funding Information: The authors thank all the patients who participated in this study. Medical writing support was provided by Parexel, with funding from Boehringer Ingelheim GmbH. Funding Information: Dragos Vinereanu received grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants and personal fees from Bristol-Myers Squibb, Pfizer, Bayer, Johnson & Johnson, and Daiichi Sankyo outside the submitted work. Dmitry Napalkov received research grants and has participated in scientific advisory boards for Boehringer Ingelheim and has received speaker’s honoraria from Bayer, Boehringer Ingelheim, Pfizer, and Takeda. Bela Benczur received speaker’s/consultancy fees from Bayer, Berlin-Chemie/Menarini, Boehringer Ingelheim, Krka Pharma, Novartis, Pfizer, Sandoz, and Sanofi. Martin Ciernik, Alexey Medvedchikov, and Wenbo Tang are employees of Boehringer Ingelheim. Pentti Põder received educational grants from Boehringer Ingelheim. Maria Trusz-Gluza received personal fees from Boehringer Ingelheim (null during the conduct of the study), personal fees and non-financial support from Boehringer Ingelheim, and personal fees from Bayer outside the submitted work. Jiří Vesely received personal fees and non-financial support from Bayer, Boehringer Ingelheim, Pfizer, MSD, and PRO.MED.CS outside the submitted work. All other authors report no conflicts of interest. Publisher Copyright: © 2021, The Author(s).Background: The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients’ perceptions of dabigatran or VKA therapy in AF. Methods: RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B). Results: Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages. Conclusions: Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe. Trial and clinical registry: Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.publishersversionPeer reviewe

«Fragility» as a predictor of bleedings in elderly patients with atrial fibrillation taking direct oral anticoagulants

The purpose of the study is to assess the contribution of senile asthenia level to hemorrhagic complications quantity in elderly patients with atrial fibrillation (AF) taking direct oral anticoagulants (DOAC).Material and methods. Elderly patients &gt;75 y.o. with AF taking dabigatran, apixaban or rivaroxaban in full or reduced dosages and without special features of bleeding (such as double and triple antithrombotic therapy) were included in the study. If a patient was under anticoagulants before the study (but not earlier than one became 75 y.o.), this experience was also analyzed. All bleedings during the first 18 months of anticoagulating were taken in mind. Patients in different DOAC groups were comparable in age and concomitant pathology. The «fragility» index was evaluated at the stage of inclusion in the study; an adapted Rockwood scale was used.Results and discussion. 102 patients with AF &gt;75 y.o. taking dabigatran, apixaban or rivaroxaban in dosages corresponding to the instructions were included in the study. During the analyzed period, 19 small clinically significant hemorrhagic events that did not require hospitalization or cancellation of DOAC were recorded. Patients with and without bleeding in anamnesis were significantly differed only by «fragility» index score (р = 0,001). The differences between concomitant pathology level which are mentioned in scale, is also not statistically significant. The average age of patients with and without bleeding anamnesis was not also significantly different (p = 0.12). In the future, it is advisable to continue the study using several scales for assessing the severity of the «fragility» index. Thus, it is advisable to calculate the «fragility» index in patients &gt;75 years of age with AF taking DOAC

Thrombodynamics Test in Assessing the Risk of Thrombus Formation in Patients with Atrial Fibrillation Taking Direct Oral Anticoagulants

Aim. To evaluate thrombus characteristics in patients with atrial fibrillation (AF) taking different direct oral anticoagulants (DOACs) using Thrombodynamics test.Materials and methods. Thrombodynamics test was performed in 100 patients with paroxysmal and permanent forms of AF taking different DOACs, dose choice was done in accordance with the instructions for drugs use. For analysis samples of fresh citrated platelet-free plasma were taken just before regular DOACs dose intake (trough concentration). Statistical data processing was carried out using R software packages.Results. All patients had no history of thrombosis or bleeding before inclusion in this study. All parameters of Thrombodynamics test taken at residual concentration of DOACs were in general within reference values, that is in the area of normal coagulation: spatial clot growth rate (V) – 26.56 (25.0; 29.2) μm/min, the time to the start of clot growth (Tlag) – 1.05 (0.85; 1.27) min, initial spatial clot growth rate (Vi) – 44.3±7.7 μm/min, stationary spatial clot growth rate (Vst) – 26.5 (24.9; 28.4) μm/min, clot size (CS) – 999.7 (912.9; 1084.7) μm, clot density (D) – 22883.1±3199.9 arb. units. D was appeared to be higher in women [22947.7 (21477.5; 22947.7) vs men [22124.8 (19722.8; 22124.8), p=0.035] and Tlag was significantly higher in patients with chronic heart failure [1.2 (1.0; 1.2) vs 1.0 (0.8; 1.0), p=0.008]. A correlation was found between level of creatinine and Tlag parameter, glomerular filtration rate (GFR) and clot density. With an increase in the level of creatinine in the blood and a decrease in GFR, respectively, there was an increase in Tlag parameter (p-value 0.038); with an increase in GFR, clot density decrease (p-value 0.005).Conclusion. All parameters of Thrombodynamics test on residual concentration of DOACs were within reference values that indicated optimal anticoagulant effect of all DOACs. The obtained data of normal coagulation at the residual concentration of the anticoagulant are consistent with the previously obtained data on the safety and effectiveness of DOACs using other methods. Further studies with clinical end points are needed to assess the clinical value of this method

Risk of Venous Thromboembolic Complications in Patients with Atrial Fibrillation: a Systematic Review and Meta-analysis

Aim: The aim of this meta-analysis and systematic review was to evaluate the possible connection between AF and VTE.Material and methods. Atrial fibrillation (AF) and atrial flutter (AFL) contribute to intra-atrial blood stasis which leads to thrombus formation with its embolization. There is some evidence that AF can be a risk factor for deep vein thrombosis (DVT) and pulmonary embolism (PE). The following databases were searched: PubMed (MEDLINE), EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials. The time frame for conducting a systematic literature search ranged from January 1, 1990 to November 1, 2021. The diagnosis of atrial fibrillation had to be confirmed by using ECG. The diagnosis of VTE could be made with Doppler imaging, ventilation/perfusion scan, CT angiography, venography, angiography or autopsy. Only the three studies with 102192 patients meeting the requirement were included in the meta-analysis.Results. The prevalence of DVT and PE were assessed using incidence rate ratios (IRR) method of the inverse variance random effects model and its 95% confidence interval (CI). The significant association between atrial fibrillation and pulmonary embolism was found (IRR, 4.18 95% Cl 1.958.98). Also there is obvious association between DVT and AF (IRR, 2.97 95% Cl 2.18-4.03).Conclusion. It can be concluded that the increased risk of developing VTE is associatedwith concomitant AF