<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2017-10-60-64</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-1868</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>ЭПИЛЕПСИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EPILEPSY</subject></subj-group></article-categories><title-group><article-title>ЛЕВЕТИРАЦЕТАМ В ЛЕЧЕНИИ ЭПИЛЕПСИИ СОБСТВЕННЫЙ ОПЫТ ПРИМЕНЕНИЯ У ВЗРОСЛЫХ  ПАЦИЕНТОВ</article-title><trans-title-group xml:lang="en"><trans-title>LEVETIRACETAM IN TREATMENT OF EPILEPSY, OWN  EXPERIENCE OF APPLICATION IN ADULT PATIENTS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Торопина</surname><given-names>Г. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Toropina</surname><given-names>G. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медиинских наук</p></bio><bio xml:lang="en"><p>MD</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Клиника нервных болезней  им. А.Я. Кожевникова Первого Московского государственного медицинского университета им. И.М. Сеченова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Sechenov’s First Moscow State Medical University, Clinic of Nervous Diseases named after A.Ya. Kozhevnikov</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>25</day><month>05</month><year>2017</year></pub-date><volume>0</volume><issue>10</issue><fpage>60</fpage><lpage>64</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Торопина Г.Г., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Торопина Г.Г.</copyright-holder><copyright-holder xml:lang="en">Toropina G.G.</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://www.med-sovet.pro/jour/article/view/1868">https://www.med-sovet.pro/jour/article/view/1868</self-uri><abstract><p>Описаны основные свойства леветирацетама  (ЛЕВ) и проанализирован  собственный опыт его применения в дозе  500–4000  мг/сут у 95 пациентов в возрасте 17–69 лет (средний возраст 34 ± 13 лет) с различными эпилептическими синдромами. Общий эффект ЛЕВ составил  69,1%, ремиссия не менее года была достигнута у 43,6%, у 17% – в течение 3 и более лет. Наилучший результат наблюдался  при юношеской миоклонической  эпилепсии – улучшение у 83,3% пациентов, ремиссия на монотерапии ЛЕВ у 75%. Высокая эффективность также отмечалась при идиопатической генерализованной и симптоматической эпилепсии – улучшение в 78,6 и 81,3% случаев соответственно. При идиопатической фокальной эпилепсии ЛЕВ показал меньшую эффективность – 51,5%. Нежелательные эффекты наблюдались у 12 пациентов (12,8%), из них только у 3 ЛЕВ был заменен по причине развития апатии, астении и появления афатических нарушений в результате аггравации фокальных приступов. В остальных случаях наблюдались сонливость, раздражительность и усиление немотивированной агрессивности, эти побочные явления прошли в течение первого месяца лечения. Полученные результаты подтверждают высокую эффективность и хорошую переносимость ЛЕВ.</p></abstract><trans-abstract xml:lang="en"><p>Basic properties of Levetiracetam (LEV) were described and own experience of its application at the dose of 500–4000 mg/day in 95 patients at the age of 17–69 years (mean age 34 ± 13 years) with various epileptic syndromes was analyzed. The overall effect of LEV made 69.1%, remission at least a year was achieved in 43.6%, in 17% – for 3 years or more. The best result was observed in juvenile myoclonic epilepsy an improvement in 83.3% of patients, remission on LEV monotherapy in 75% of patients. High efficiency was also noted in idiopathic and symptomatic generalized epilepsy – an improvement making up 78.6 and 81.3%, respectively. Idiopathic focal epilepsy LEO showed less efficiency – about 51.5%. Adverse effects were observed in 12 patients (12,8%), of which only in 3 the LEV was replaced because of the development of apathy, fatigue and the appearance of efficiency violations as a result of aggravate focal seizures. In other cases drowsiness, irritability and increased unprovoked aggression were observed, these side effects passed within the first month of treatment. The obtained results confirm the high efficacy and good tolerability of LEV.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>леветирацетам</kwd><kwd>идиопатическая генерализованная эпилепсия</kwd><kwd>юношеская миоклоническая эпилепсия</kwd><kwd>идиопатическая фокальная эпилепсия</kwd><kwd>симптоматическая эпилепсия</kwd><kwd>взрослые пациенты</kwd><kwd>эффективность</kwd><kwd>нежелательные эффекты</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Levetiracetam</kwd><kwd>idiopathic generalized epilepsy</kwd><kwd>juvenile myoclonic epilepsy</kwd><kwd>idiopathic focal epilepsy</kwd><kwd>symptomatic epilepsy</kwd><kwd>adult patients</kwd><kwd>efficacy</kwd><kwd>adverse effects</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Löscher W, Hönack D. Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. Eur. J. Pharmacol., 1993, 232: 147-158.</mixed-citation><mixed-citation xml:lang="en">Löscher W, Hönack D. Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. Eur. J. Pharmacol., 1993, 232: 147-158.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Gower AJ, Hirsch E, Boehrer A, Noyer M, Marescaux C. Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy. Epilepsy Res, 1995, 22: 207-213.</mixed-citation><mixed-citation xml:lang="en">Gower AJ, Hirsch E, Boehrer A, Noyer M, Marescaux C. Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy. Epilepsy Res, 1995, 22: 207-213.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Klitgaard H, Matagne A, Gobert J, Wülfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur. J. Pharmacol., 1998, 353: 191-206.</mixed-citation><mixed-citation xml:lang="en">Klitgaard H, Matagne A, Gobert J, Wülfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur. J. Pharmacol., 1998, 353: 191-206.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Noyer M, Gillard M, Matagne A, Hénichart JP, Wülfert E. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur. J. Pharmacol., 1995, 286: 137-146.</mixed-citation><mixed-citation xml:lang="en">Noyer M, Gillard M, Matagne A, Hénichart JP, Wülfert E. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur. J. Pharmacol., 1995, 286: 137-146.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl. Acad. Sci. USA, 2004, 101: 9861-9866.</mixed-citation><mixed-citation xml:lang="en">Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl. Acad. Sci. USA, 2004, 101: 9861-9866.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia, 2002, 43: 9-18.</mixed-citation><mixed-citation xml:lang="en">Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia, 2002, 43: 9-18.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rigo JM, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, Leprince P, Moonen G, Selak I, Matagne A, Klitgaard H. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABAand glycine-gated currents. Br. J. Pharmacol., 2002, 136: 659-672.</mixed-citation><mixed-citation xml:lang="en">Rigo JM, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, Leprince P, Moonen G, Selak I, Matagne A, Klitgaard H. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABAand glycine-gated currents. Br. J. Pharmacol., 2002, 136: 659-672.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Niespodziany I, Klitgaard H, Margineanu DG. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci. Lett., 2001, 306: 5-8.</mixed-citation><mixed-citation xml:lang="en">Niespodziany I, Klitgaard H, Margineanu DG. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci. Lett., 2001, 306: 5-8.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Glass GA, Stankiewicz J, Mithoefer A, Freeman R, Bergethon PR. Levetiracetam for seizures after liver transplantation. Neurology, 2005, 64: 1084-1085.</mixed-citation><mixed-citation xml:lang="en">Glass GA, Stankiewicz J, Mithoefer A, Freeman R, Bergethon PR. Levetiracetam for seizures after liver transplantation. Neurology, 2005, 64: 1084-1085.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Zaatreh MM. Levetiracetam in porphyric status epilepticus: a case report. Clin. Neuropharmacol., 2005, 28: 243-244.</mixed-citation><mixed-citation xml:lang="en">Zaatreh MM. Levetiracetam in porphyric status epilepticus: a case report. Clin. Neuropharmacol., 2005, 28: 243-244.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Brockmöller J, Thomsen T, Wittstock M, Coupez R, Lochs H, Roots I. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin. Pharmacol. Ther., 2005, 77: 529-541.</mixed-citation><mixed-citation xml:lang="en">Brockmöller J, Thomsen T, Wittstock M, Coupez R, Lochs H, Roots I. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin. Pharmacol. Ther., 2005, 77: 529-541.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Зенков Л.Р. Кеппра в лечении эпилепсии. М.: Пресс-сервис, 2007.</mixed-citation><mixed-citation xml:lang="en">Зенков Л.Р. Кеппра в лечении эпилепсии. М.: Пресс-сервис, 2007.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Abou-Khalil B.W. Levetiracetam Efficacy in Idiopathic Generalized Epilepsy: Long Suspected and Now Confirmed in Randomized Clinical Trials. Epilepsy Curr., 2008, 8: 16-18.</mixed-citation><mixed-citation xml:lang="en">Abou-Khalil B.W. Levetiracetam Efficacy in Idiopathic Generalized Epilepsy: Long Suspected and Now Confirmed in Randomized Clinical Trials. Epilepsy Curr., 2008, 8: 16-18.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Verrotti A, Cerminara C, Coppola G, Franzoni E, Parisi P, Iannetti P, Aloisi P, Tozzi E, Cusmai R, Vigevano F, Chiarelli F, Curatolo P. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev. Med. Child. Neurol., 2008, 50: 29-32.</mixed-citation><mixed-citation xml:lang="en">Verrotti A, Cerminara C, Coppola G, Franzoni E, Parisi P, Iannetti P, Aloisi P, Tozzi E, Cusmai R, Vigevano F, Chiarelli F, Curatolo P. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev. Med. Child. Neurol., 2008, 50: 29-32.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Alhamrani М, Babtain F, Bhatia H, Velmurugan M. Comparison of Levetiracetam With Sodium Valproate in Controlling Seizure in Patients Suffering From Juvenile Myoclonic Epilepsy. Jentashapir. J. Health Res, 2014, 5(4): e21875.</mixed-citation><mixed-citation xml:lang="en">Alhamrani М, Babtain F, Bhatia H, Velmurugan M. Comparison of Levetiracetam With Sodium Valproate in Controlling Seizure in Patients Suffering From Juvenile Myoclonic Epilepsy. Jentashapir. J. Health Res, 2014, 5(4): e21875.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Sirven JI, Drazkowski JF. Levetiracetam. Wyllie’s Treatment of Epilepsy: Principles and Practice (5th ed). Eds.: Wyllie E, Cascino GD, Gidal BE, Goodkin HP. Phyladelphia: Lippincott Williams &amp; Wilkins, 2011: 731-735.</mixed-citation><mixed-citation xml:lang="en">Sirven JI, Drazkowski JF. Levetiracetam. Wyllie’s Treatment of Epilepsy: Principles and Practice (5th ed). Eds.: Wyllie E, Cascino GD, Gidal BE, Goodkin HP. Phyladelphia: Lippincott Williams &amp; Wilkins, 2011: 731-735.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Карлов В.А., Власов П.Н., Жидкова И.А. Предварительные результаты эффективности генерического леветирацетама (эпитерра) в тонотерапии эпилепсии у взрослых пациентов. Неврология, нейропсихиатрия, психосоматика, 2015, спецвыпуск 1: 36-40.</mixed-citation><mixed-citation xml:lang="en">Карлов В.А., Власов П.Н., Жидкова И.А. Предварительные результаты эффективности генерического леветирацетама (эпитерра) в тонотерапии эпилепсии у взрослых пациентов. Неврология, нейропсихиатрия, психосоматика, 2015, спецвыпуск 1: 36-40.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Vrielynck P. Current and emerging treatments for absence seizures in young patients. Neuropsychiatr. Dis. Treat., 2013, 9: 963-975.</mixed-citation><mixed-citation xml:lang="en">Vrielynck P. Current and emerging treatments for absence seizures in young patients. Neuropsychiatr. Dis. Treat., 2013, 9: 963-975.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther. Adv. Neurol. Dis., 2009, 2: 79-91.</mixed-citation><mixed-citation xml:lang="en">Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther. Adv. Neurol. Dis., 2009, 2: 79-91.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Atmaca MM, Orhan EK, Bebek N, Gurses C. Intravenous levetiracetam treatment in status epilepticus: A prospective study. Epilepsy Res, 2015, 114: 13-22.</mixed-citation><mixed-citation xml:lang="en">Atmaca MM, Orhan EK, Bebek N, Gurses C. Intravenous levetiracetam treatment in status epilepticus: A prospective study. Epilepsy Res, 2015, 114: 13-22.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Grosso S, Cordelli DM, Franzoni E, Coppola G, Capovilla G, Zamponi N, Verrotti A, Morgese G, Balestri P. Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy. Seizure, 2007, 16: 345-350.</mixed-citation><mixed-citation xml:lang="en">Grosso S, Cordelli DM, Franzoni E, Coppola G, Capovilla G, Zamponi N, Verrotti A, Morgese G, Balestri P. Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy. Seizure, 2007, 16: 345-350.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur. J. Paediatr. Neurol., 2011, 15: 1-7.</mixed-citation><mixed-citation xml:lang="en">Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur. J. Paediatr. Neurol., 2011, 15: 1-7.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Mruk AL, Garlitz KL, Leung NR. Levetiracetam in neonatal seizures: A Review. J. Pediatr. Pharmacol. Ther., 2015, 20: 76-89.</mixed-citation><mixed-citation xml:lang="en">Mruk AL, Garlitz KL, Leung NR. Levetiracetam in neonatal seizures: A Review. J. Pediatr. Pharmacol. Ther., 2015, 20: 76-89.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology, 2013, 80: 400-405.</mixed-citation><mixed-citation xml:lang="en">Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology, 2013, 80: 400-405.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Anderson P. Lamotrigine, Levetiracetam top AEDs in pregnancy. American Epilepsy Society (AES) 2016 Annual Meeting. Poster 1.211, December, 2016.</mixed-citation><mixed-citation xml:lang="en">Anderson P. Lamotrigine, Levetiracetam top AEDs in pregnancy. American Epilepsy Society (AES) 2016 Annual Meeting. Poster 1.211, December, 2016.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia, 2005, 46: 775-777.</mixed-citation><mixed-citation xml:lang="en">Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia, 2005, 46: 775-777.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Werhahn KJ, Klimpe S, Balkaya S, Trinka E, Krämer G. The safety and efficacy of add-on levetiracetam in elderly patients with focal epilepsy: A one-year observational study. Seizure, 2011, 20: 305-311.</mixed-citation><mixed-citation xml:lang="en">Werhahn KJ, Klimpe S, Balkaya S, Trinka E, Krämer G. The safety and efficacy of add-on levetiracetam in elderly patients with focal epilepsy: A one-year observational study. Seizure, 2011, 20: 305-311.</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>
