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Обеспечение эффективности и безопасности лечебного процесса у пациентов с поясничной болью
Камчатнов П.Р., Ханмурзаева С.Б., Чугунов А.В., Ханмурзаева Н.Б. Обеспечение эффективности и безопасности лечебного процесса у пациентов с поясничной болью. Consilium Medicum. 2017; 19 (2): 146–150.
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Kamchatnov P.R., Khanmurzaeva S.B., Chugunov A.V., Khanmurzaeva N.B. Maintenance of efficiency and safety of medical process of patients with a lumbar pain. Consilium Medicum. 2017; 19 (2): 146–150.
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Аннотация
Поясничная боль (ПБ) представляет собой наиболее распространенный тип скелетно-мышечных болевых синдромов. Вне зависимости от причин ее возникновения ПБ ассоциирована с длительными сроками временной утраты трудоспособности, снижением качества жизни пациентов, значительными материальными затратами на лечение и восстановительные мероприятия. Лечение пациентов с ПБ может вести к развитию нежелательных побочных эффектов, возникновение которых связано с рядом причин, важными среди которых являются выбор и использование неадекватных комбинаций препаратов, превышение суточных и курсовых дозировок лекарственных средств, нарушение рекомендованного врачом режима приема лекарств. Снижению риска побочных эффектов могут способствовать верная оценка клинической ситуации и адекватный выбор лекарственного препарата, строгое следование инструкции по его применению. Рассматривается возможность применения при лечения пациентов с ПБ препарата Нолодатак (флупиртин), обладающего противоболевым, миорелаксирующим и нейропротективным эффектами. Анализируются показания и ограничения к его назначению, возможные риски проводимой терапии.
Ключевые слова: поясничная боль, скелетно-мышечные болевые синдромы, флупиртин, Нолодатак, лечение, гепатотоксичность.
Ключевые слова: поясничная боль, скелетно-мышечные болевые синдромы, флупиртин, Нолодатак, лечение, гепатотоксичность.
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Low back pain (LBP) is the most common type of musculoskeletal pain syndrome. Regardless of the reasons for its occurrence, the LBP is associated with long periods of temporary disability, a decrease in the quality of life of patients, significant material costs of treatment and rehabilitation measures. Treatment of patients with LBP can lead to the development of undesirable side effects, the occurrence of which is associated with a number of reasons, important among which are the selection and use of inadequate drug combinations, the excess of daily and course dosages of drugs, a violation of the recommended medication regimen. A reduction in the risk of side effects can be facilitated by a correct assessment of the clinical situation and an adequate choice of the drug, strict adherence to the instructions for its use. The possibility of using the preparation Nolodatak (flupirtine), which has analgesic, myorelaxing and neuroprotective effects, in the treatment of patients with LBP is considered. The indications and limitations to its purpose, possible risks of the therapy are analyzed.
Key words: low back pain, musculoskeletal pain syndromes, flupirtine, Nolodatak, treatment, hepatotoxicity.
Key words: low back pain, musculoskeletal pain syndromes, flupirtine, Nolodatak, treatment, hepatotoxicity.
Полный текст
Список литературы
1. Hoy D, March L, Brooks P et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 2014; 73: 968–74.
2. Mafi J, McCarthy E, Davis R, Landon B. Worsening Trends in the Management and Treatment of Back Pain. JAMA Intern Med 2013; 173 (17): 1573–81.
3. Sivasubramaniam V, Patel H, Ozdemir B et al. Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time series study. BMJ Open 2015; 5: e009011. DOI:10.1136/bmjopen-2015- 009011
4. Vos T, Flaxman A, Naghavi M et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–96.
5. Баранцевич Е., Андреев В. Возможности лечения хронической боли при пояснично-крестцовой радикулопатии. Врач. 2012; 11: 13–9. / Barantsevich E., Andreev V. Vozmozhnosti lecheniia khronicheskoi boli pri poiasnichno-kresttsovoi radikulopatii. Vrach. 2012; 11: 13–9. [in Russian]
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7. Есин Р.Г., Лотфуллина Н.З., Есин О.Р. Цервикалгия, дорзалгия, люмбалгия. Дифференциальная диагностика, дифференцированная терапия. Казань: ИИЦ УД Президента РТ, 2015. / Esin R.G., Lotfullina N.Z., Esin O.R. Tservikalgiia, dorzalgiia, liumbalgiia. Differentsial'naia diagnostika, differentsirovannaia terapiia. Kazan': IITs UD Prezidenta RT, 2015. [in Russian]
8. Ueberall A, Eberhardt A, Mueller-Schwefe H. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice. Int J Gen Med 2016; 9: 39–51.
9. Qaseem A, Wilt T, McLean R et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; DOI: 10.7326/M16-2367
10. Brown D, Passmore G. Neural KCNQ (Kv7) channels. Br J Pharmacol 2009; 156 (8): 1185–95.
11. Rivera-Arconada I, Vicente-Baz J, Lopez-Garcia J. Targeting Kv7 channels in pain pathways. Oncotarget 2017; DOI: 10.18632/oncotarget.15261
12. Szelenyi I. Flupirtine, a re-discovered drug, revisited. Inflamm Res 2013; 62 (3): 251–8.
13. Fleckenstein J, Sittl R, Averbeck B et al. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo – therapeutic potential for peripheral neuropathies: results of a randomised controlled trial. J Transl Med 2013; 11: 34–9.
14. Kornhuber J, Bleich S, Wiltfang J et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J Neural Transm 1999; 106 (9–10): 857–67.
15. Klinger F, Bajric M, Salzer I et al. d-Subunit-containing GABAA receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172 (20): 4946–58.
16. Klinger F, Geier P, Dorostkar M et al. Concomitant facilitation of GABAA receptors and KV7 channels by the non-opioid analgesic flupirtine. Br J Pharmacol 2012; 166: 1631–42.
17. Harish S, Bhuvana K, Bengalorkar M, Kumar T. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Klawe C, Maschke M. Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound. Expert Opin Pharmacother 2009; 10 (9): 1495–500.
19. Bientinesi R, Mancuso C, Martire M et al. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression. Naunyn Schmiedebergs Arch Pharmacol 2017; 390 (2): 127–37.
20. Takagi H, Hashitani H. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder. Eur J Pharmacol 2016; 789: 179–86.
21. Ahuja V, Mitra S, Kazal S, Huria A. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial. Indian J Anaesth 2015; 59 (7): 411–5.
22. Mueller-Schwefe G. Flupirtine in acute and chronic pain associated with muscle tenseness. Results of a postmarket surveillance study. Fortschr Med Orig 2003; 121 (1): 11–8.
23. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10):1617–34.
24. Worz R, Stroehmann I. Ruckemschmerzen: Leitlinien der medicamentosen therapie. Munch Med Wschr 2000; 142: 27–33.
25. Камчатнов П.Р., Батышева Т.Т., Ганжула П.А. и др. Применение катадолона у больных со спондилогенной дорсопатией. Журн. неврологии и психиатрии им. С.С.Корсакова. 2006; 106 (11): 46–9. / Kamchatnov P.R., Batysheva T.T., Ganzhula P.A. i dr. Primenenie katadolona u bol'nykh so spondilogennoi dorsopatiei. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2006; 106 (11): 46–9. [in Russian]
26. Douros A, Bronder E, Andersohn F et al. Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study. Br J Clin Pharmacol 2015; 79 (6): 988–99.
27. Michel M, Radziszewski P, Falconer C et al. Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years. Br J Clin Pharmacol 2012; 73 (5): 821–5.
28. Nicoletti P, Werk A, Sawle A et al. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenet Genomics 2016; 26 (5): 218–24.
29. Wörz R. Longterm treatment of chronic pain patients with flupirtine on hepatotoxicity and persistent effectiveness from 7 months to 22 years. MMW Fortschr Med 2014; 156 (Suppl. 4): 127–34.
30. Burkhardt H, Wehling M. Non-opioid pain medication in the elderly. Schmerz 2015; 29 (4): 371–9.
2. Mafi J, McCarthy E, Davis R, Landon B. Worsening Trends in the Management and Treatment of Back Pain. JAMA Intern Med 2013; 173 (17): 1573–81.
3. Sivasubramaniam V, Patel H, Ozdemir B et al. Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time series study. BMJ Open 2015; 5: e009011. DOI:10.1136/bmjopen-2015- 009011
4. Vos T, Flaxman A, Naghavi M et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–96.
5. Баранцевич Е., Андреев В. Возможности лечения хронической боли при пояснично-крестцовой радикулопатии. Врач. 2012; 11: 13–9. / Barantsevich E., Andreev V. Vozmozhnosti lecheniia khronicheskoi boli pri poiasnichno-kresttsovoi radikulopatii. Vrach. 2012; 11: 13–9. [in Russian]
6. Насонов Е.Л., Яхно Н.Н., Каратеев А.Е. и др. Общие принципы лечения скелетно-мышечной боли: междисциплинарный консенсус. Научно-практическая ревматология. 2016; 54 (3): 247–65. / Nasonov E.L., Yakhno N.N., Karateev A.E. i dr. Obshchie printsipy lecheniia skeletno-myshechnoi boli: mezhdistsiplinarnyi konsensus. Nauchno-prakticheskaia revmatologiia. 2016; 54 (3): 247–65. [in Russian]
7. Есин Р.Г., Лотфуллина Н.З., Есин О.Р. Цервикалгия, дорзалгия, люмбалгия. Дифференциальная диагностика, дифференцированная терапия. Казань: ИИЦ УД Президента РТ, 2015. / Esin R.G., Lotfullina N.Z., Esin O.R. Tservikalgiia, dorzalgiia, liumbalgiia. Differentsial'naia diagnostika, differentsirovannaia terapiia. Kazan': IITs UD Prezidenta RT, 2015. [in Russian]
8. Ueberall A, Eberhardt A, Mueller-Schwefe H. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice. Int J Gen Med 2016; 9: 39–51.
9. Qaseem A, Wilt T, McLean R et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; DOI: 10.7326/M16-2367
10. Brown D, Passmore G. Neural KCNQ (Kv7) channels. Br J Pharmacol 2009; 156 (8): 1185–95.
11. Rivera-Arconada I, Vicente-Baz J, Lopez-Garcia J. Targeting Kv7 channels in pain pathways. Oncotarget 2017; DOI: 10.18632/oncotarget.15261
12. Szelenyi I. Flupirtine, a re-discovered drug, revisited. Inflamm Res 2013; 62 (3): 251–8.
13. Fleckenstein J, Sittl R, Averbeck B et al. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo – therapeutic potential for peripheral neuropathies: results of a randomised controlled trial. J Transl Med 2013; 11: 34–9.
14. Kornhuber J, Bleich S, Wiltfang J et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J Neural Transm 1999; 106 (9–10): 857–67.
15. Klinger F, Bajric M, Salzer I et al. d-Subunit-containing GABAA receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172 (20): 4946–58.
16. Klinger F, Geier P, Dorostkar M et al. Concomitant facilitation of GABAA receptors and KV7 channels by the non-opioid analgesic flupirtine. Br J Pharmacol 2012; 166: 1631–42.
17. Harish S, Bhuvana K, Bengalorkar M, Kumar T. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Klawe C, Maschke M. Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound. Expert Opin Pharmacother 2009; 10 (9): 1495–500.
19. Bientinesi R, Mancuso C, Martire M et al. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression. Naunyn Schmiedebergs Arch Pharmacol 2017; 390 (2): 127–37.
20. Takagi H, Hashitani H. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder. Eur J Pharmacol 2016; 789: 179–86.
21. Ahuja V, Mitra S, Kazal S, Huria A. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial. Indian J Anaesth 2015; 59 (7): 411–5.
22. Mueller-Schwefe G. Flupirtine in acute and chronic pain associated with muscle tenseness. Results of a postmarket surveillance study. Fortschr Med Orig 2003; 121 (1): 11–8.
23. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10):1617–34.
24. Worz R, Stroehmann I. Ruckemschmerzen: Leitlinien der medicamentosen therapie. Munch Med Wschr 2000; 142: 27–33.
25. Камчатнов П.Р., Батышева Т.Т., Ганжула П.А. и др. Применение катадолона у больных со спондилогенной дорсопатией. Журн. неврологии и психиатрии им. С.С.Корсакова. 2006; 106 (11): 46–9. / Kamchatnov P.R., Batysheva T.T., Ganzhula P.A. i dr. Primenenie katadolona u bol'nykh so spondilogennoi dorsopatiei. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2006; 106 (11): 46–9. [in Russian]
26. Douros A, Bronder E, Andersohn F et al. Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study. Br J Clin Pharmacol 2015; 79 (6): 988–99.
27. Michel M, Radziszewski P, Falconer C et al. Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years. Br J Clin Pharmacol 2012; 73 (5): 821–5.
28. Nicoletti P, Werk A, Sawle A et al. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenet Genomics 2016; 26 (5): 218–24.
29. Wörz R. Longterm treatment of chronic pain patients with flupirtine on hepatotoxicity and persistent effectiveness from 7 months to 22 years. MMW Fortschr Med 2014; 156 (Suppl. 4): 127–34.
30. Burkhardt H, Wehling M. Non-opioid pain medication in the elderly. Schmerz 2015; 29 (4): 371–9.
________________________________________________
1. Hoy D, March L, Brooks P et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 2014; 73: 968–74.
2. Mafi J, McCarthy E, Davis R, Landon B. Worsening Trends in the Management and Treatment of Back Pain. JAMA Intern Med 2013; 173 (17): 1573–81.
3. Sivasubramaniam V, Patel H, Ozdemir B et al. Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time series study. BMJ Open 2015; 5: e009011. DOI:10.1136/bmjopen-2015- 009011
4. Vos T, Flaxman A, Naghavi M et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–96.
5. Barantsevich E., Andreev V. Vozmozhnosti lecheniia khronicheskoi boli pri poiasnichno-kresttsovoi radikulopatii. Vrach. 2012; 11: 13–9. [in Russian]
6. Nasonov E.L., Yakhno N.N., Karateev A.E. i dr. Obshchie printsipy lecheniia skeletno-myshechnoi boli: mezhdistsiplinarnyi konsensus. Nauchno-prakticheskaia revmatologiia. 2016; 54 (3): 247–65. [in Russian]
7. Esin R.G., Lotfullina N.Z., Esin O.R. Tservikalgiia, dorzalgiia, liumbalgiia. Differentsial'naia diagnostika, differentsirovannaia terapiia. Kazan': IITs UD Prezidenta RT, 2015. [in Russian]
8. Ueberall A, Eberhardt A, Mueller-Schwefe H. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice. Int J Gen Med 2016; 9: 39–51.
9. Qaseem A, Wilt T, McLean R et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; DOI: 10.7326/M16-2367
10. Brown D, Passmore G. Neural KCNQ (Kv7) channels. Br J Pharmacol 2009; 156 (8): 1185–95.
11. Rivera-Arconada I, Vicente-Baz J, Lopez-Garcia J. Targeting Kv7 channels in pain pathways. Oncotarget 2017; DOI: 10.18632/oncotarget.15261
12. Szelenyi I. Flupirtine, a re-discovered drug, revisited. Inflamm Res 2013; 62 (3): 251–8.
13. Fleckenstein J, Sittl R, Averbeck B et al. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo – therapeutic potential for peripheral neuropathies: results of a randomised controlled trial. J Transl Med 2013; 11: 34–9.
14. Kornhuber J, Bleich S, Wiltfang J et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J Neural Transm 1999; 106 (9–10): 857–67.
15. Klinger F, Bajric M, Salzer I et al. d-Subunit-containing GABAA receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172 (20): 4946–58.
16. Klinger F, Geier P, Dorostkar M et al. Concomitant facilitation of GABAA receptors and KV7 channels by the non-opioid analgesic flupirtine. Br J Pharmacol 2012; 166: 1631–42.
17. Harish S, Bhuvana K, Bengalorkar M, Kumar T. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Klawe C, Maschke M. Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound. Expert Opin Pharmacother 2009; 10 (9): 1495–500.
19. Bientinesi R, Mancuso C, Martire M et al. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression. Naunyn Schmiedebergs Arch Pharmacol 2017; 390 (2): 127–37.
20. Takagi H, Hashitani H. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder. Eur J Pharmacol 2016; 789: 179–86.
21. Ahuja V, Mitra S, Kazal S, Huria A. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial. Indian J Anaesth 2015; 59 (7): 411–5.
22. Mueller-Schwefe G. Flupirtine in acute and chronic pain associated with muscle tenseness. Results of a postmarket surveillance study. Fortschr Med Orig 2003; 121 (1): 11–8.
23. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10):1617–34.
24. Worz R, Stroehmann I. Ruckemschmerzen: Leitlinien der medicamentosen therapie. Munch Med Wschr 2000; 142: 27–33.
25. Kamchatnov P.R., Batysheva T.T., Ganzhula P.A. i dr. Primenenie katadolona u bol'nykh so spondilogennoi dorsopatiei. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2006; 106 (11): 46–9. [in Russian]
26. Douros A, Bronder E, Andersohn F et al. Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study. Br J Clin Pharmacol 2015; 79 (6): 988–99.
27. Michel M, Radziszewski P, Falconer C et al. Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years. Br J Clin Pharmacol 2012; 73 (5): 821–5.
28. Nicoletti P, Werk A, Sawle A et al. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenet Genomics 2016; 26 (5): 218–24.
29. Wörz R. Longterm treatment of chronic pain patients with flupirtine on hepatotoxicity and persistent effectiveness from 7 months to 22 years. MMW Fortschr Med 2014; 156 (Suppl. 4): 127–34.
30. Burkhardt H, Wehling M. Non-opioid pain medication in the elderly. Schmerz 2015; 29 (4): 371–9.
Авторы
П.Р.Камчатнов*1, С.Б.Ханмурзаева2, А.В.Чугунов1, Н.Б.Ханмурзаева2
1 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1;
2 ФГБОУ ВО «Дагестанский государственный медицинский университет». 367000, Россия, Махачкала, пл. Ленина, д. 1
*pavkam7@gmail.com
1 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1;
2 ФГБОУ ВО «Дагестанский государственный медицинский университет». 367000, Россия, Махачкала, пл. Ленина, д. 1
*pavkam7@gmail.com
________________________________________________
P.R.Kamchatnov*1, S.B.Khanmurzaeva2, A.V.Chugunov1, N.B.Khanmurzaeva2
1 N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1;
2 Dagestan State Medical University. 367000, Russian Federation, Makhachkala, pl. Lenina, d. 1
*pavkam7@gmail.com
1 N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1;
2 Dagestan State Medical University. 367000, Russian Federation, Makhachkala, pl. Lenina, d. 1
*pavkam7@gmail.com
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