Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial
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01.12.2021 |
Alexeeva E.
Horneff G.
Dvoryakovskaya T.
Denisova R.
Nikishina I.
Zholobova E.
Malievskiy V.
Santalova G.
Stadler E.
Balykova L.
Spivakovskiy Y.
Kriulin I.
Alshevskaya A.
Moskalev A.
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Pediatric Rheumatology |
10.1186/s12969-020-00488-9 |
0 |
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© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
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Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial
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01.12.2021 |
Alexeeva E.
Horneff G.
Dvoryakovskaya T.
Denisova R.
Nikishina I.
Zholobova E.
Malievskiy V.
Santalova G.
Stadler E.
Balykova L.
Spivakovskiy Y.
Kriulin I.
Alshevskaya A.
Moskalev A.
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Pediatric Rheumatology |
10.1186/s12969-020-00488-9 |
0 |
Ссылка
© 2021, The Author(s). Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
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Ultrathin Langmuir–Schaefer films of slipped-cofacial J-type phthalocyanine dimer: Supramolecular organization, UV/Vis/NIR study and nonlinear absorbance of femtosecond laser radiation
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15.04.2021 |
Kazak A.V.
Marchenkova M.A.
Khorkov K.S.
Kochuev D.A.
Rogachev A.V.
Kholodkov I.V.
Usol'tseva N.V.
Savelyev M.S.
Tolbin A.Y.
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Applied Surface Science |
10.1016/j.apsusc.2021.148993 |
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© 2021 Elsevier B.V. Based on a comprehensive theoretical and experimental approach, a low-defect thin film of stable dimeric phthalocyanine zinc complex (bis-[2-hydroxy-9(10),16(17), 23(24)-tri-tert-butylphthalocyanine]zinc – J-[OHPctZn]2) was prepared. It is shown that the dye forms stable amorphous edge-on monolayers at the air/water interface with an insignificant content of cylindrical 3D aggregates. These floating layers keep their structure when transferred by the Langmuir-Schaefer method onto a solid substrate, demonstrating a tendency towards ordered H-aggregation with preserving their linear molecular properties. Mixed two- and three-photon absorption of femtosecond laser pulses (280 fs) was firstly detected on this sample, as well as the ability of a material to the nonlinear attenuation of the intense irradiation, which is important for optical limiting.
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Novel octabromo-substituted lanthanide(III) phthalocyanines – Prospective compounds for nonlinear optics
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01.02.2021 |
Kuzmina E.A.
Dubinina T.V.
Vasilevsky P.N.
Saveliev M.S.
Gerasimenko A.Y.
Borisova N.E.
Tomilova L.G.
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Dyes and Pigments |
10.1016/j.dyepig.2020.108871 |
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© 2020 Elsevier Ltd Novel octabromo-substituted lanthanide(III) phthalocyanines were obtained via template method starting from corresponding 4,5-dibromophthalonitrile and identified by high-resolution mass-spectrometry, 1H nuclear magnetic resonanse and infra red spectroscopy. To achieve an initial 4,5-dibromophthalonitrile the reaction conditions of Pd(0) catalyzed cyanation were optimized. The peripheral bromine atoms impact on the optical properties of phthalocyanine complexes. The bathochromic shift of the main absorption band (Q band) was observed going from unsubstituted to octachloro- and then to octabromo-substituted phthalocyanines. All complexes demonstrated nonlinear optical responses in the DMF solution. Increasing the intensity of laser radiation leads to a nonlinear decrease in transmittance and further restoration of optical properties when switching back to linear mode. Nonlinear optical responses depend on the central ion nature. Europium phthalocyanine showed the enhanced nonlinear absorption coefficient compared to lutetium and terbium complexes. This was caused by an enhanced population of excited state and faster excitement for complexes with large central ions. The impact of peripheral bromine groups into nonlinear optical properties was determined through the comparison with unsubstituted analogues.
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Molecular characteristics of uveal melanoma and intraocular tumors (Review)
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01.01.2021 |
KATOPODIS P.
KHALIFA M.S.
ANIKIN V.
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Oncology Letters |
10.3892/ol.2020.12270 |
0 |
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© 2021 Spandidos Publications. All rights reserved. Malignant melanomas within the eye present different types of metabolic and metastatic behavior. Uveal melanoma (UM) affects a quarter of a million individuals in the USA; however, the molecular pathogenesis is not well understood. Although UV radiation is a risk factor in cutaneous melanomas, it is not crucial for UM progression. Apart from chromosomal abnormalities, numerous major tumorigenic signaling pathways, including the PI3K/Akt, MAPK/ERK, Ras-association domain family 1 isoform A and Yes-associated protein/transcriptional co-activator with PDZ-binding motif signaling pathways, are associated with intraocular tumors. The present review describes the current insights regarding these signaling pathways that regulate the cell cycle and apoptosis, and could be used as potential targets for the treatment of UMs.
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Dynamics of concomitant therapy in children with juvenile idiopathic arthritis treated with etanercept and methotrexate
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01.10.2019 |
Alexeeva E.
Dvoryakovskaya T.
Denisova R.
Sleptsova T.
Isaeva K.
Chomahidze A.
Fetisova A.
Mamutova A.
Alshevskaya A.
Gladkikh V.
Moskalev A.
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Pediatrics and Neonatology |
10.1016/j.pedneo.2019.02.003 |
2 |
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© 2019 Background: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. Methods: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). Results: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. Conclusion: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.
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The role of adjuvant radiotherapy after surgery for upper and lower urinary tract urothelial carcinoma: A systematic review
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01.10.2019 |
Iwata T.
Kimura S.
Abufaraj M.
Janisch F.
Karakiewicz P.
Seebacher V.
Rouprêt M.
Nasu Y.
Shariat S.
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Urologic Oncology: Seminars and Original Investigations |
10.1016/j.urolonc.2019.05.021 |
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© 2019 Elsevier Inc. Objectives: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. Materials and method: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. Results: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. Conclusions: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.
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Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method
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03.09.2019 |
Alexeeva E.
Dvoryakovskaya T.
Denisova R.
Sleptsova T.
Isaeva K.
Chomahidze A.
Fetisova A.
Mamutova A.
Alshevskaya A.
Gladkikh V.
Moskalev A.
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Modern Rheumatology |
10.1080/14397595.2018.1516329 |
1 |
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© 2018, © 2018 Japan College of Rheumatology. Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3–6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3–9) months (p =.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p =.045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.
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Modern ideas about juvenile dermatomyositis part 2: Activity assessment and treatment
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01.09.2019 |
Podchernyaeva N.
Konevina M.
Tikhaya M.
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Pediatriya - Zhurnal im G.N. Speranskogo |
10.24110/0031-403X-2019-98-5-135-146 |
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© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.
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Neutropenia during tocilizumab treatment is not associated with infection risk in systemic or polyarticular-course juvenile idiopathic arthritis
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01.09.2019 |
Pardeo M.
Wang J.
Ruperto N.
Alexeeva E.
Chasnyk V.
Schneider R.
Horneff G.
Huppertz H.
Minden K.
Onel K.
Zemel L.
Martin A.
Koné-Paut I.
Siamopoulou-Mavridou A.
Silva C.
Porter-Brown B.
Bharucha K.
Brunner H.
De Benedetti F.
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Journal of Rheumatology |
10.3899/jrheum.180795 |
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© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.
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A Rational Approach for Obtaining High-Specific Polyclonal Antibodies against Recombinant Alpha-Synuclein
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01.10.2018 |
Barinova K.
Melnikova A.
Schmalhausen E.
Muronetz V.
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Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry |
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© 2018, Pleiades Publishing, Ltd. Abstract: An approach for quick and efficient production of polyclonal antibodies to the target antigen, alpha-synuclein, has been proposed. Two methods have been employed to purify specific rabbit polyclonal antibodies against recombinant human alpha-synuclein, produced by subcutaneous immunization with complete Freund’s adjuvant. It was shown that purification on CNBr-activated Sepharose with immobilized alpha-synuclein resulted in antibody preparation with rabbit serum histidine-rich glycoprotein as a contaminant. Two-stage antibody purification procedure first on Sepharose with immobilized protein G, and then on alpha-synuclein immobilized column helps to avoid contamination and to obtain homogenous antibody preparation. Antibodies recognize different conformations of alpha-synuclein and can be used in a variety of immunochemical approaches, including immunocytochemistry.
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Growth during tocilizumab therapy for polyarticular-course juvenile idiopathic arthritis: 2-year data from a phase III clinical trial
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01.08.2018 |
Bharucha K.
Brunner H.
Penadés I.
Nikishina I.
Rubio-Pérez N.
Oliveira S.
Kobusinska K.
Schmeling H.
Sztajnbok F.
Weller-Heinemann F.
Zholobova E.
Zulian F.
Allen R.
Chaitow J.
Frane J.
Wells C.
Ruperto N.
De Benedetti F.
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Journal of Rheumatology |
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1 |
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Copyright © 2018. All rights reserved. Objective: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial. Methods: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104. Mean ± SD height velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were measured in patients receiving ≥ 1 dose of TCZ who did not receive growth hormone and in patients whose baseline Tanner stage was ≤ 3. Results: The study included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 ± 1.2, which was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and r = -0.12, respectively). There were 123 patients at Tanner stage ≤ 3 at baseline, among whom 103 completed the study with 2 years of height SDS data. Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of 103 patients (72%), height SDS was greater than at baseline, and mean height velocity was 6.7 ± 2.0 cm/year. Conclusion. Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.
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Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial
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01.07.2018 |
Opoka-Winiarska V.
Żuber Z.
Alexeeva E.
Chasnyk V.
Nikishina I.
Dębowska G.
Smolewska E.
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Clinical Rheumatology |
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2 |
Ссылка
© 2018, The Author(s). Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.
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Approaches to Pharmaceutical Analysis of an Innovative Liposomal Preparation for Treating Hepatitis C
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01.06.2018 |
Smirnov V.
Krasnykh L.
Shilovskii I.
Ryzhenkova A.
Khaitov M.
Drozdov V.
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Pharmaceutical Chemistry Journal |
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0 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The composite Y14/siUTR, a complex consisting of cationic lipopeptide Y14 as an excipient and pharmaceutical substance of small interfering RNAtargeted against the UTR region of hepatitis C virus (siUTR), was investigated. The composite was intended to inhibit the hepatitis C virus replication cycle. The present work was aimed at developing pharmaceutical analytical methods for the components of this composite using HPLC-UV and UV spectroscopy.
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Risk factors for growth retardation in patients with juvenile scleroderma
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01.05.2018 |
Bokareva E.
Podchernyaeva N.
Vitebskaya A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Objective of the research: to dentify risk factors for growth retardation in patients with juvenile scleroderma (JSD). The presented data show that the most unfavorable factors for growth retardation in patients with JSD are the systemic form of the disease, debut age less than 4 years. Other unfavorable factors of growth retardation developing are father's height less than 175 cm and a mother's height less than 165 cm. Analysis of the effect of glucocorticoid saverage daily dose during the year on the growth rate in patients with JSD, normalization of growth rates was noted with its decrease to 0,2 mg/kg/day or less.
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Selection and switching of genetically engineered biological agents in treatment of juvenile arthritis
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01.05.2018 |
Zholobova E.
Ignatova A.
Seylanova N.
Golubeva A.
Shpitonkova O.
Afonina E.
Nikolaeva M.
Chebysheva S.
Meleshkina A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Therapy with genetically engineered biological preparations (GEBP) significantly improved the prognosis and quality of life of patients with juvenile idiopathic arthritis (JIA). However, primary or secondary in efficiency, the development of undesirable phenomena require switching to another GEBP. Objective of the research – to determine optimal GEBP preparations when selecting and switching therapy based on the analysis of prescribed GEBP in real practice, depending on the clinical version of the JIA and the presence of uveitis. Materials and methods: the study included 322 patients with JIA on GEBP therapy, observed in the Pediatric Rheumatology Department of Children's Clinical Hospital of the I.M. Sechenov First Moscow State Medical University from Jan. 1, 2015 to Dec. 31, 2017. Retrospective, continuous observational clinical study. Of 322 patients, 70 (21,74%) had systemic JIA, 155 patients (48,14%) had polyarterial seronegative for rheumatoid factor (RF–) variant of JIA, 9 patients (2,8%) – polyarticular seropositive for rheumatoid factor RF+) variant of JIA, 55 patients (17,08%) – oligoarticular (persistent and spreading) variant of JIA, 26 patients (8,07%) – enthesitis (juvenile spondylitis), 7 patients (2,17%) – psoriatic variant of JIA. Results: as the first biological preparation were prescribed: etanercept to 177 (54,97%) patients; adalimumab to 51 (15,84%); tocilizumab to 44 (13,66%); abatacept to 39 (12,11%); infliximab to 11 (3,42%) patients. Transition to the second line of biological therapy was performed in 51 patients (in 15,8% of cases), on the third line of therapy in 13 patients (in 4,04% of cases), on the fourth line in 3 patients (in 0,93% of cases). As the second-line GEBP adelimumab was prescribed in 22 cases (43,14%), tocilizumab in 13 (25,49%), etanercept in 11 (21,57%), abatacept in 5 (9,8%). GEBP inefficiency was the reason for switching to the second line in 32 cases (9,9%). Of these, secondary inefficiency in 22 cases (6,8%); primary inefficiency – in 4 (1,3%), low efficiency – in 6 (1,9%), development/exacerbation of uveitis – in 7 patients (2,2%), in 6 cases (1,9%) due to insufficient compliance, drug shortage in the community, etc. Adverse effects caused switching in 5 patients (1,6%), incl. in 4 children – infusion reactions, in one – tuberculosis. Analysis of GEBP choice depending on the disease form and the presence of uveitis, was performed in 3 groups. Group 1 (n=70) consisted of patients with systemic JIA. Group 2 (n=53) included patients with articular form of JIA and concomitant uveitis. Group 3 (n=199) included patients with articular form of JIA without concomitant uveitis. Patients with systemic JIA as the first-line GEBP tocilizumab was prescribed significantly more often – to 38 patients out of 70 (54,29±5,96%) than etanercept – to 19 patients (27,14±10,19%) (t=2, 3, p<0,05), and other drugs in total (infliximab, abatacept, adalimumab) – to 13 (18,57±10,88%) (t=2,9, p<0,05). Switching to GEBP second line in this group was performed in 20 patients (28,57%). Tocilizumab was the final choice drug (after 3 years of follow-up) at the time of samples collection in 50 patients (71,43%) with systemic JIA. In patients with articular forms of JIA and concomitant uveitis as the first-line GEBP, adalimumab was prescribed significantly more often – in 34 of 53 cases (64,15±8,23%) than other drugs (abatacept, etanercept, infliximab) in total – 19 of 53 cases (35,85±11,01%) (t=2,06, p<0,05). Adalimumab was the drug final choice at the time of sample collection for 43 (81,13%) patients with JIA and uveitis. Most patients with articular form without uveitis received etanercept as first-line GEBP, 150 of 199 (75,38±3,54%), and etanercept prescription frequency was significantly higher than that of other drugs (abatacept, adalimumab, tocilizumab, infliximab) in total – 49 of 199 (24,62±6,19%) (t=7,1, p<0,01). In this group, the switching frequency was the smallest and amounted only 8,54%. The number of patients who received etanercept at the end of the study actually remained unchanged – 148 patients (74,37%).
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Anti-Inflammatory Action of Polyextract of Orthosiphon stamineus (Leaves), Arctostaphylos uva-ursi (Leaves), Polygonum aviculare (Herbs), Calendula officinalis (Flowers), and Glycyrrhiza uralensis (Root) on the Rat Prostate
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01.05.2018 |
Nikolaev S.
Nikolaeva G.
Mondodoev A.
Markaryan A.
Nikolaeva I.
Nagaslaeva O.
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Pharmaceutical Chemistry Journal |
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0 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A polyextract consisting of the extracts of the five title plants shows a marked prostate-protective effect in experimental chronic prostatitis. The pharmacotherapeutic efficacy of the phytoextract gives a basis to recommend its use in complex treatment and prophylaxis of prostatitis.
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Assessing Ge-132 as an antioxidant in organic and water-containing media
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01.03.2018 |
Vishtorskaya A.
Saverina E.
Pechennikov V.
Krylova I.
Lalov A.
Syroeshkin M.
Egorov M.
Jouikov V.
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Journal of Organometallic Chemistry |
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3 |
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© 2018 The antioxidant activity of Ge-132 (2-carboxyethylgermanium sesquioxide, [(O 0.5 ) 3 GeCH 2 CH 2 COOH] n ), a widely used organic germanium dietary supplement, was assessed by cyclic voltammetry and through its interaction with a stable radical 2,2,-diphenyl-1-picrylhydrazyl (DPPH) monitored by UV-Vis and EPR spectroscopy in water, CH 3 CN, DMF, MeOH, and their mixtures with water. The results obtained by these methods are coherent in that Ge-132 can manifest its antioxidant activity only in the absence of water because the latter hydrolyses its Ge-O-Ge fragment responsible for quenching free radicals. Thus, contrary to a common use of Ge-132 as a water-soluble agent, it can act as an antioxidant solely in a lipid environment, which is important for understanding the mechanism of its biological activity.
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Use of nonbiologic treatments in antihistamine-refractory chronic urticaria: a review of published evidence
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02.01.2018 |
Holm J.
Ivyanskiy I.
Thomsen S.
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Journal of Dermatological Treatment |
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6 |
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© 2017 Informa UK Limited, trading as Taylor & Francis Group. Background: Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria. Methods: We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety. Results: We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG. Conclusion: The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments’ future recommendation in selected patients.
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Arzhaans as part of the cultural and religious landscape of the republic of tuva
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01.01.2018 |
Kopeliovich G.
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New Research of Tuva |
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0 |
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© 2018 New Reaearch of Tuva. All rights reserved. Tuvinian healing springs, Arzhaans, are examined in this article as an important part of the cultural and religious landscape of the republic. Their importance and the interest in them, displayed by both the local population, primarily Tuvans, and visitors to the region, have been reinforced in the process of contemporary cultural revival. Our study is based on the theoretical and methodological approach of anthropology, which studies the cultural landscape as a space which includes natural objects endowed by man with a certain cultural meaning, changing due to the anthropogenic impact. Methodologically, we rely on the works on the role and place of water sources in cultures, and specifically of arzhaans in Tuva culture. Other sources include the results of the author's field studies in Tuva in 2017-2018 (most importantly, ofs interview with Tuvans). Arzhaans represent a part of the cultural and religious landscape of Tuva, which has its own center, a special shrine - a healing spring. Around this center rise a number of traditional rituals, connecting man with nature, generations of the present with the past, focusing on healing of the body and soul. The cult of arzhaans also performs an identification function, allowing Tuvans to realize their tribal, ethnocultural identity. Scientific studies made by chemists and hydrologists prove the healing properties of arzhaans. This reinforces the faith of the population and visitors in the usefulness of arzhaan tours, which helps advance a suggestion that arzhaans can act as centers of tourist interest.
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