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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">cardiovascular</journal-id><journal-title-group><journal-title xml:lang="ru">Кардиоваскулярная терапия и профилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Cardiovascular Therapy and Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1728-8800</issn><issn pub-type="epub">2619-0125</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15829/1728-8800-2019-4-25-32</article-id><article-id custom-type="elpub" pub-id-type="custom">cardiovascular-860</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ИНФАРКТ МИОКАРДА</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>MYOCARDIAL INFARCTION</subject></subj-group></article-categories><title-group><article-title>Внутригоспитальная смена блокатора P2Y12 у больных инфарктом миокарда с подъемом сегмента ST в условиях реальной клинической практики: влияние на состояние функциональной активности тромбоцитов и тромбоцитопоэза, прогностическое значение</article-title><trans-title-group xml:lang="en"><trans-title>Intrahospital switch of the P2Y12 inhibitors in patients with ST segment elevation myocardial infarction in ‘real-life’ clinical practice: the effect on the functional activity of thrombocytes and thrombocytopoiesis, prognostic value</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0951-9314</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Малинова</surname><given-names>Л. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Malinova</surname><given-names>L. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Малинова Лидия Игоревна — доктор медицинских наук, заведующая отделом атеросклероза и хронической ишемической болезни сердца НИИ кардиологии, профессор кафедры терапии и геронтологии ИДПО.</p><p>Саратов.</p><p>Тел.: +7 (905) 322­35­34</p></bio><bio xml:lang="en"><p>Saratov.</p></bio><email xlink:type="simple">lidia.malinova@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7515-1722</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Долотовская</surname><given-names>П. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Dolotovskaya</surname><given-names>P. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Долотовская Полина Владимировна — кандидат медицинских наук, научный сотрудник отдела неотложной и инвазивной кардиологии НИИ кардиологии.</p><p>Саратов.</p></bio><bio xml:lang="en"><p>Saratov.</p></bio><email xlink:type="simple">nikalpol@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5029-1131</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пучиньян</surname><given-names>Н. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Puchinyan</surname><given-names>N. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Пучиньян Никита Филиппович — кандидат медицинских наук, научный сотрудник отдела атеросклероза и хронической ишемической болезни сердца НИИ кардиологии.</p><p>Саратов.</p></bio><bio xml:lang="en"><p>Saratov.</p></bio><email xlink:type="simple">puchin@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5686-6431</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фурман</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Furman</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Фурман Николай Викторович — кандидат медицинских наук, заведующий отделом неотложной и инвазивной кардиологии НИИ кардиологии.</p><p>Саратов.</p></bio><bio xml:lang="en"><p>Saratov.</p></bio><email xlink:type="simple">furman.nikolay@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Саратовский государственный медицинский университет имени В.И. Разумовского Минздрава России</institution></aff><aff xml:lang="en"><institution>V.I. Razumovsky Saratov State Medical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>04</day><month>09</month><year>2019</year></pub-date><volume>18</volume><issue>4</issue><fpage>25</fpage><lpage>32</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Малинова Л.И., Долотовская П.В., Пучиньян Н.Ф., Фурман Н.В., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Малинова Л.И., Долотовская П.В., Пучиньян Н.Ф., Фурман Н.В.</copyright-holder><copyright-holder xml:lang="en">Malinova L.I., Dolotovskaya P.V., Puchinyan N.F., Furman V.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://cardiovascular.elpub.ru/jour/article/view/860">https://cardiovascular.elpub.ru/jour/article/view/860</self-uri><abstract><sec><title>Цель</title><p>Цель. Характеризовать смену блокатора P2Y12 у больных инфарктом миокарда с подъемом сегмента ST (HM↑ST) в условиях реальной клинической практики, дать клиническую оценку функциональному состоянию тромбоцитов и тромбоцитопоэза и определить клинико-прогностическое значение смены блокатора P2Y12 в рамках двойной антиагрегантной терапии у больных HM↑ST.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Проведено локальное, стратифицированное, проспективное исследование, в которое был вовлечен 101 пациент, госпитализированный не позднее 12 ч с момента манифестации HM↑ST. Анализировалась антиагрегантная терапия (ААТ), назначаемая лечащими врачами на догоспитальном и стационарном этапах лечения. В динамике исследовали функциональную активность тромбоцитов, уровни тромбопоэтина (TPO), фактора стромальных клеток 1 (SDF1) и тромбопоэтиного рецептора (MPL). Минимальный период наблюдения составил 2 года. Отслеживались наступление летального исхода и повторные госпитализации вследствие кардиоваскулярных причин.</p></sec><sec><title>Результаты</title><p>Результаты. Замена блокаторов P2Y12 проводилась у 32,7% пациентов с HM[if gte msEquation 12]&gt;&lt;m:oMath&gt;&lt;i&#13;
 style='mso-bidi-font-style:normal'&gt;&lt;span style='font-size:14.0pt;line-height:&#13;
 107%;font-family:"Cambria Math","serif"'&gt;&lt;m:r&gt;↑&lt;/m:r&gt;&lt;/span&gt;&lt;/i&gt;&lt;/m:oMath&gt;&lt;![endif][if !msEquation][endif]ST. Чаще всего в стационаре проводили замену клопидогрела, назначенного на догоспитальном этапе, тикагрелором (ранняя эскалация ААТ) — 22,8%. У пациентов с ранней эскалацией ААТ к седьмым сут. происходило достоверно большая ингибиция агрегационной активности тромбоцитов (p=0,005), однако по ряду параметров: угол наклона кривой агрегации, латентное время агрегации и площадь под кривой агрегации, выявлена активация коллаген-индуцированной агрегации тромбоцитов. При ранней эскалации ААТ уровень TPO был статистически достоверно выше, как на вторые, так и на 7 сут. измерения: 256,2 (209,0; 396,8) пг/мл vs 137,5 (105,7; 179,1) пг/мл (p=0,000) и 283,4 (228,9; 334,3) пг/мл vs 226,5 (163,2; 287,3) пг/мл (p=0,045), соответственно. Частота достижения комбинированной конечной точки (летальный исход + повторные госпитализации) была 7,9% у пациентов, которым проводили замену P2Y12, и 28,1% у пациентов, которым блокатор P2Y12 не меняли.</p></sec><sec><title>Заключение</title><p>Заключение. В реальной клинической практике у пациентов с HM↑ST наиболее часто проводилась ранняя эскалация ААТ, которая характеризовалась более выраженным подавлением аденозин-дифосфат-индуцированной агрегации и секреции тромбоцитов, чем у пациентов без замены блокатора P2Y12, но активацией коллаген-индуцированной агрегации. Выявлено усиление тромбоцитогенеза в условиях ранней замены клопидогрела на тикагрелор. Внутригоспитальная замена блокатора P2Y12 у больных HM↑ST независимо от ее варианта сопровождалась снижением двухлетнего риска летального исхода и повторных госпитализаций. </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. To assess the P2Y12 inhibitors switch in patients ST segment elevation myocardial infarction (STEMI) in real-life’ clinical practice, evaluate the functional activity of thrombocytes and thrombocytopoiesis and determine the clinical and prognostic value of P2Y12 inhibitors switch in the framework of dual antiplatelet therapy in patients with STEMI.</p></sec><sec><title>Material and methods</title><p>Material and methods. We conducted local, stratified, prospective study in which were involved 101 patients, hospitalized no later than 12hours after the STEMI manifestation. The antiplatelet therapy (APT), prescribed by the physicians at the pre-hospital and inpatient phases of treatment, was analyzed. Functional activity of thrombocytes, levels of thrombopoietin (THPO), stromal cell-derived factor 1 (SDF1) and thrombopoietic receptor (MPL) were investigated. The minimum observation period was 2 years. Death and repeated hospitalizations due to cardiovascular causes were monitored.</p></sec><sec><title>Results</title><p>Results. P2Y12 inhibitors were switched in 32,7% of patients with STEMI. In the hospital, clopidogrel, which was prescribed at the prehospital phase, was replaced with ticagrelor (early APT escalation) — 22,8%. Patients with early APT escalation by the seventh day had significantly greater inhibition of platelet aggregation activity parameters (slope of the aggregation curve, latent aggregation time and area under the aggregation curve). Activation of the collagen-induced platelet aggregation was detected. With the early escalation of APT, the THPO level was statistically significantly higher, both on the second and on the 7th day measurements: 256,2 (209,0; 396,8) pg/ml vs 137,5 (105,7; 179,1) pg/ml (p=0,000) and 283,4 (228,9; 334,3) pg/ml vs 226,5 (163,2; 287,3) pg/ml (p=0,045), respectively. The frequency of reaching the combined endpoint (death + re-hospitalization) was 7,9% in patients who had a P2Y12 switch, and 28,1% in patients who did not change the P2Y12 blocker.</p></sec><sec><title>Conclusion</title><p>Conclusion. In actual clinical practice, patients with STEMI had the most frequent early APT escalation, which was characterized by a more significant suppression of adenosine diphosphate-induced platelet aggregation and secretion than in patients without P2Y12 inhibitors switch, but with activation of collagen-induced aggregation. An increase in thrombocytogenesis was revealed in early replacement of clopidogrel by ticagrelor. Intrahospital replacement of the P2Y12 inhibitor in patients with STEMI was accompanied by a decrease in the two-year death risk and repeated hospitalizations.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>антиагрегантная терапия</kwd><kwd>замена блокатора P2Y12</kwd><kwd>тромбоциты</kwd><kwd>тромбопоэтин</kwd><kwd>инфаркт миокарда</kwd></kwd-group><kwd-group xml:lang="en"><kwd>antiplatelet therapy</kwd><kwd>P2Y12 inhibitors switch</kwd><kwd>thrombocytes</kwd><kwd>thrombopoietin</kwd><kwd>myocardial infarction</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при финансовой поддержке РФФИ в рамках научного проекта № 17-04-00070</funding-statement><funding-statement xml:lang="en">The study was conducted with the financial support of the Russian Foundation for Basic Research in the framework of the research project № 17-04-00070.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Руда М. Я., Аверков О. В., Комаров А. Л. и др. О возможностях ослабления интенсивности антитромбоцитарной терапии у больных после острого коронарного синдрома резолюция совета экспертов общества специалистов по неотложной кардиологии. Неотложная кардиология. 2017:44-5.</mixed-citation><mixed-citation xml:lang="en">Ruda MJ, Averkov OB, Komarov AL, et al. On the possibilities of weakening the 9. intensity of antiplatelet therapy in patients after acute coronary syndrome resolving the information of experts on emergency cardiology. Emergency cardiology. 2017;44-5. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Angiolillo DJ, Rollini F, Storey RF, et al. International Expert Consensus on Switching Platelet P2Yi2 Receptor-Inhibiting Therapies. Circulation. 2017;136:1955-75. doi:10.1161/CIRCULATIONAHA.118.033779.</mixed-citation><mixed-citation xml:lang="en">Angiolillo DJ, Rollini F, Storey RF, et al. International Expert Consensus on Switching Platelet P2Yi2 Receptor-Inhibiting Therapies. Circulation. 2017;136:1955-75. doi:10.1161/CIRCULATIONAHA.118.033779.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Naziroglu, M. TRPM2 channel membrane currents in primary rat megakaryocytes were activated by the agonist ADP-ribose but not oxidative stress. J Membr Biol. 2011 May;241(2):51-7. doi:10.1007/s00232-011-9356-8.</mixed-citation><mixed-citation xml:lang="en">Naziroglu, M. TRPM2 channel membrane currents in primary rat megakaryocytes were activated by the agonist ADP-ribose but not oxidative stress. J Membr Biol. 2011 May;241(2):51-7. doi:10.1007/s00232-011-9356-8.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Ibanez B, James S, Agewall S et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevationThe Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017:ehx393-ehx393. doi:10.1093/eurheartj/ehx393.</mixed-citation><mixed-citation xml:lang="en">Ibanez B, James S, Agewall S et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevationThe Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017:ehx393-ehx393. doi:10.1093/eurheartj/ehx393.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Alexopoulos D, Xanthopoulou I, Deftereos S, et al. In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome. Am Heart J. 2014;167:68-76 e2. doi:10.1016/j.ahj.2013.10.010.</mixed-citation><mixed-citation xml:lang="en">Alexopoulos D, Xanthopoulou I, Deftereos S, et al. In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome. Am Heart J. 2014;167:68-76 e2. doi:10.1016/j.ahj.2013.10.010.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Biscaglia S, Campo G, Pavasini R, et al. Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry. Platelets. 2016;27:484-7. doi:10.3109/09537104.2015.1119815.</mixed-citation><mixed-citation xml:lang="en">Biscaglia S, Campo G, Pavasini R, et al. Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry. Platelets. 2016;27:484-7. doi:10.3109/09537104.2015.1119815.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X, Xi S, Liu J, et al. Switching between ticagrelor and clopidogrel in patients who underwent percutaneous coronary intervention: insight into contemporary practice in Chinese patients. European heart journal supplements. J Eur Society of Cardiology. 2016;18:F19-26. doi:10.1093/eurheartj/suw034.</mixed-citation><mixed-citation xml:lang="en">Wang X, Xi S, Liu J, et al. Switching between ticagrelor and clopidogrel in patients who underwent percutaneous coronary intervention: insight into contemporary practice in Chinese patients. European heart journal supplements. J Eur Society of Cardiology. 2016;18:F19-26. doi:10.1093/eurheartj/suw034.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">De Luca L, D'Ascenzo F, Musumeci G, et al. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry. EuroIntervention. 2017;13:459-66. doi:10.4244/EIJ-D-17-00092.</mixed-citation><mixed-citation xml:lang="en">De Luca L, D'Ascenzo F, Musumeci G, et al. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry. EuroIntervention. 2017;13:459-66. doi:10.4244/EIJ-D-17-00092.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Оганов P. Г, Лепахин В. К., Фитилев С. Б. и др. Оценка выполнения рекомендаций по вторичной профилактике сердечно-сосудистых заболеваний у пациентов, перенесших инфаркт миокарда (фармакоэпидемиологическое исследование). Кардиоваскулярная терапия и профилактика. 2009;8(4):71-5.</mixed-citation><mixed-citation xml:lang="en">Oganov PG, Lepakhin VK, Fitilev SB, et al. Assessing the implementation of the recommendations on secondary cardiovascular prevention in patients after myocardial infarction (a pharmaco-epidemiologic study). Cardiovascular Therapy and Prevention. 2009;8(4):71-5. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Rollini F, Franchi F, Angiolillo DJ. Switching P2Y!2-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13:11-27. doi: 10.1038/nrcardio.2015.113.</mixed-citation><mixed-citation xml:lang="en">Rollini F, Franchi F, Angiolillo DJ. Switching P2Y!2-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13:11-27. doi: 10.1038/nrcardio.2015.113.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Rollini F, Franchi F, Cho JR, et al. A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J. 2016;37:2722-30. doi:10.1093/eurheartj/ehv744.</mixed-citation><mixed-citation xml:lang="en">Rollini F, Franchi F, Cho JR, et al. A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J. 2016;37:2722-30. doi:10.1093/eurheartj/ehv744.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010;121:1188-99. doi:10.1161/CIRCULATIONAHA.109.919456.</mixed-citation><mixed-citation xml:lang="en">Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010;121:1188-99. doi:10.1161/CIRCULATIONAHA.109.919456.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Тавлуева Е. В., Ярковская А. П., Алексеенко А. В. и др. Гипоагрегационный эффект у больных инфарктом миокарда с подъемом сегмента st при замене клопидогрела на тикагрелор. Атеротромбоз. 2016;54-60. doi:10.21518/2307-1109-2016-2-54-60.</mixed-citation><mixed-citation xml:lang="en">Tavlueva EB, Yarkovskaya AP, Alekseenko AV, et al. Hypoaggregatory effect in patients with myocardial infarction with the rise of the segment st when replacing clopidogrel with ticagrelor. Atherothrombosis. 2016;54-60. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Malinova L, Furman N, Dolotovskaya P, et al. Thrombopoeitin as a biomarker and a regulatory mediator in acute heart failure. Eur J Heart Failure. 2018;20:112. doi:10.1002/ejhf.1197.</mixed-citation><mixed-citation xml:lang="en">Malinova L, Furman N, Dolotovskaya P, et al. Thrombopoeitin as a biomarker and a regulatory mediator in acute heart failure. Eur J Heart Failure. 2018;20:112. doi:10.1002/ejhf.1197.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Носовский А. М., Пихлак А. Э., Логачев В. А. и др. Статистика малых выборок в медицинских исследованиях. Российский медицинский журнал. 2013:57-60.</mixed-citation><mixed-citation xml:lang="en">Nosovsky AM, Pihlak AE, Logachev VA, et al. Statistics of small samples in medical research. Russian Medical Journal 2013: 57-60. (In Russ.)</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
