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Современные возможности лечения симптомов хронической венозной недостаточности нижних конечностей: от патогенетических механизмов к реальной клинической практике
Современные возможности лечения симптомов хронической венозной недостаточности нижних конечностей: от патогенетических механизмов к реальной клинической практике
Кудыкин М.Н. Современные возможности лечения симптомов хронической венозной недостаточности нижних конечностей: от патогенетических механизмов к реальной клинической практике. Consilium Medicum. Хирургия (Прил.). 2015; 2: 17–20.
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Аннотация
Симптомы хронических заболеваний вен нижних конечностей – разнообразны и многочисленны, но одним из основных является болевой синдром, определяющий снижение качества жизни пациентов. В статье изложены современные представления о формировании болевых ощущений при хронических заболеваниях вен нижних конечностей, рассмотрены основные патогенетические механизмы формирования болевого синдрома, особое внимание уделено возможностям современной фармакотерапии в лечении этого патологического состояния. Показано, что практически все патогенетические механизмы формирования так называемого синдрома венозной боли могут быть купированы применением очищенной микронизированной флавоноидной фракции, раскрываются основные действующие механизмы флавоноидов, способствующие купированию болевых ощущений. Приводятся доказательства, полученные в ходе крупных клинических испытаний.
Ключевые слова: флавоноиды, биофлавоноиды, хронические заболевания вен, диосмин, микронизированная очищенная флавоноидная фракция.
Key words: flavonoids, bioflavonoids, chronic diseases of veins, diosmin, Moffitt, micronized purified flavonoid fraction.
Ключевые слова: флавоноиды, биофлавоноиды, хронические заболевания вен, диосмин, микронизированная очищенная флавоноидная фракция.
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Key words: flavonoids, bioflavonoids, chronic diseases of veins, diosmin, Moffitt, micronized purified flavonoid fraction.
Полный текст
Список литературы
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2. Jawien A, Grzela T, Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicentre cross-sectional study in 40095 patients. Phlebology 2003; 81: 110–22.
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8. Wrona M, Jöckel KH, Pannier F et al. Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. Eur J Vasc Endovasc Surg 2015; 50 (3): 360–7. doi: 10.1016/j.ejvs.2015.05.013. Epub 2015.
9. Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467.
10. Klement W, Arndt JO. Pain but no temperature sensation are evoked by termal stimulation of cutaneous veins in man. Neurosci Lett 1991; 123: 119–22.
11. Klement W, Arndt JO. Adenosine does not evoke pain from venous and paravascular nociceptors in the human. Cardivasc Res 1992; 26: 186–9.
12. Badier-Commandier C, Jacob MP, Michel JB. Le remodelage variqueux. Medecine Therapeutique 2006; 6: 718–23.
13. Boisseau MR. Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. Clin Hemorheol Microcirc 2007; 37 (3): 277–90. Review.
14. Danziger N. Pathophysiology of pain in venous disease. Phlebolymphology 2008; 15: 107–14.
15. Howlader MH, Smith PD. Symptoms of chronic venous disease and association with systemic inflammatory markers. J Vasc Surg 2003; 38: 950–4.
16. Padberg FT, Maniker AH, Carmel G et al. Sensory Impairment: a feature of chronic venous in-sufficiency. J Vasc Surg 1999; 30: 836–42.
17. Ramelet A-A, Boisseau MR, Allegra C et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: Current medical position, prospective views and final resolution. Clin Hemorheology Microcirculation 2005; 33: 309–19.
18. Bergan J, Scmid-Schonbein G, Coleridge-Smith Ph et al. Chronic Venous Disease. N Engl J Med 2006; 355: 488–98.
19. Шлякова А.А., Корнева К.Г., Кудыкин М.Н., Перетягин П.В. Особенности микроциркуляции нижних конечностей у пациентов с сахарным диабетом 2 типа в сочетании с хронической венозной недостаточностью. Терапевт. 2014; 1: 15–8. / Shliakova A.A., Korneva K.G., Kudykin M.N., Peretiagin P.V. Osobennosti mikrotsirkuliatsii nizhnikh konechnostei u patsientov s sakharnym diabetom 2 tipa v sochetanii s khronicheskoi venoznoi nedostatochnost'iu. Terapevt. 2014; 1: 15–8. [in Russian]
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21. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. Int Angiology 2008; 27: 1–59.
22. Ramelet A-A, Perrin M, Kern P, Bounameaux H. Phlebology, 5-th edition. Elsevier Masson, 2008; p. 565.
23. Davies AH. Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015. pii: S1078–5884(15)00699-1. doi: 10.1016/j.ejvs.2015.09.024
24. Varicose Veins in the Legs: The Diagnosis and Management of Varicose Veins. National Clinical Guideline Centre (UK). London: National Institute for Health and Care Excellence (UK), 2013.
25. Российские клинические рекомендации по диагностике и лечению хронических заболеваний вен. Утверждено совещанием экспертов 10.02.2013. Флебология. 2013; 2: 6–47. / Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu khronicheskikh zabolevanii ven. Utverzhdeno soveshchaniem ekspertov 10.02.2013. Flebologiia. 2013; 2: 6–47. [in Russian]
26. Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol 2005; 3 (1): 1–9. Review.
27. Jantet G. RELIEF Study Group. Chronic Venous Insufficiency: Worlwide Results of the RELIEF Study. Angiology 2002; 53: 245–56.
28. Rabe E, Agus GB, Roztocil K. Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial. Int Angiol 2015; 34 (5): 428–36. Epub 2015.
29. Pitsch F. Assessment of treatment efficacy on venous symptoms: the example of Detralex. Phlebolymphology 2008; 15: 137–42.
30. Belczak SQ, Sincos IR, Campos W et al. Veno-active drugs for chronic venous disease: A randomized, double-blind, placebo-controlled parallel-design trial. Phlebology 2014; 29 (7): 454–60. doi: 10.1177/0268355513489550. Epub 2013.
31. Colerige-Smith P, Lok C, Ramelet AA. Venous leg ulcer: meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg 2005; 30: 198–208.
2. Jawien A, Grzela T, Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicentre cross-sectional study in 40095 patients. Phlebology 2003; 81: 110–22.
3. Langer RD, Ho E, Deneberg JO et al. Relation-ship between symptoms and venous disease. Arch Int Med 2005; 165: 1420–4.
4. Labropoulos N, Stansby G. Venous and Lymphatic Diseases. Taylor & Francis, 2006; p. 559.
5. Eklof B, Perrin M, Konstantinos T. Delis et al. Up-date terminology of chronic venous disorders: The VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg 2009; 49: 498–501.
6. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. International Angiology 2008; 27: 1–59.
7. Bradbury A, Evans C, Allan P et al. What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ 1999; 318: 353–6.
8. Wrona M, Jöckel KH, Pannier F et al. Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. Eur J Vasc Endovasc Surg 2015; 50 (3): 360–7. doi: 10.1016/j.ejvs.2015.05.013. Epub 2015.
9. Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467.
10. Klement W, Arndt JO. Pain but no temperature sensation are evoked by termal stimulation of cutaneous veins in man. Neurosci Lett 1991; 123: 119–22.
11. Klement W, Arndt JO. Adenosine does not evoke pain from venous and paravascular nociceptors in the human. Cardivasc Res 1992; 26: 186–9.
12. Badier-Commandier C, Jacob MP, Michel JB. Le remodelage variqueux. Medecine Therapeutique 2006; 6: 718–23.
13. Boisseau MR. Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. Clin Hemorheol Microcirc 2007; 37 (3): 277–90. Review.
14. Danziger N. Pathophysiology of pain in venous disease. Phlebolymphology 2008; 15: 107–14.
15. Howlader MH, Smith PD. Symptoms of chronic venous disease and association with systemic inflammatory markers. J Vasc Surg 2003; 38: 950–4.
16. Padberg FT, Maniker AH, Carmel G et al. Sensory Impairment: a feature of chronic venous in-sufficiency. J Vasc Surg 1999; 30: 836–42.
17. Ramelet A-A, Boisseau MR, Allegra C et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: Current medical position, prospective views and final resolution. Clin Hemorheology Microcirculation 2005; 33: 309–19.
18. Bergan J, Scmid-Schonbein G, Coleridge-Smith Ph et al. Chronic Venous Disease. N Engl J Med 2006; 355: 488–98.
19. Shliakova A.A., Korneva K.G., Kudykin M.N., Peretiagin P.V. Osobennosti mikrotsirkuliatsii nizhnikh konechnostei u patsientov s sakharnym diabetom 2 tipa v sochetanii s khronicheskoi venoznoi nedostatochnost'iu. Terapevt. 2014; 1: 15–8. [in Russian]
20. Schmid-Schonbein GW, Granger DN. Molecular Basis for Microcirculatory Disorders. Springer, 2003; p. 640.
21. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. Int Angiology 2008; 27: 1–59.
22. Ramelet A-A, Perrin M, Kern P, Bounameaux H. Phlebology, 5-th edition. Elsevier Masson, 2008; p. 565.
23. Davies AH. Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015. pii: S1078–5884(15)00699-1. doi: 10.1016/j.ejvs.2015.09.024
24. Varicose Veins in the Legs: The Diagnosis and Management of Varicose Veins. National Clinical Guideline Centre (UK). London: National Institute for Health and Care Excellence (UK), 2013.
25. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu khronicheskikh zabolevanii ven. Utverzhdeno soveshchaniem ekspertov 10.02.2013. Flebologiia. 2013; 2: 6–47. [in Russian]
26. Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol 2005; 3 (1): 1–9. Review.
27. Jantet G. RELIEF Study Group. Chronic Venous Insufficiency: Worlwide Results of the RELIEF Study. Angiology 2002; 53: 245–56.
28. Rabe E, Agus GB, Roztocil K. Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial. Int Angiol 2015; 34 (5): 428–36. Epub 2015.
29. Pitsch F. Assessment of treatment efficacy on venous symptoms: the example of Detralex. Phlebolymphology 2008; 15: 137–42.
30. Belczak SQ, Sincos IR, Campos W et al. Veno-active drugs for chronic venous disease: A randomized, double-blind, placebo-controlled parallel-design trial. Phlebology 2014; 29 (7): 454–60. doi: 10.1177/0268355513489550. Epub 2013.
31. Colerige-Smith P, Lok C, Ramelet AA. Venous leg ulcer: meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg 2005; 30: 198–208.
2. Jawien A, Grzela T, Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicentre cross-sectional study in 40095 patients. Phlebology 2003; 81: 110–22.
3. Langer RD, Ho E, Deneberg JO et al. Relation-ship between symptoms and venous disease. Arch Int Med 2005; 165: 1420–4.
4. Labropoulos N, Stansby G. Venous and Lymphatic Diseases. Taylor & Francis, 2006; p. 559.
5. Eklof B, Perrin M, Konstantinos T. Delis et al. Up-date terminology of chronic venous disorders: The VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg 2009; 49: 498–501.
6. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. International Angiology 2008; 27: 1–59.
7. Bradbury A, Evans C, Allan P et al. What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ 1999; 318: 353–6.
8. Wrona M, Jöckel KH, Pannier F et al. Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. Eur J Vasc Endovasc Surg 2015; 50 (3): 360–7. doi: 10.1016/j.ejvs.2015.05.013. Epub 2015.
9. Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467.
10. Klement W, Arndt JO. Pain but no temperature sensation are evoked by termal stimulation of cutaneous veins in man. Neurosci Lett 1991; 123: 119–22.
11. Klement W, Arndt JO. Adenosine does not evoke pain from venous and paravascular nociceptors in the human. Cardivasc Res 1992; 26: 186–9.
12. Badier-Commandier C, Jacob MP, Michel JB. Le remodelage variqueux. Medecine Therapeutique 2006; 6: 718–23.
13. Boisseau MR. Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. Clin Hemorheol Microcirc 2007; 37 (3): 277–90. Review.
14. Danziger N. Pathophysiology of pain in venous disease. Phlebolymphology 2008; 15: 107–14.
15. Howlader MH, Smith PD. Symptoms of chronic venous disease and association with systemic inflammatory markers. J Vasc Surg 2003; 38: 950–4.
16. Padberg FT, Maniker AH, Carmel G et al. Sensory Impairment: a feature of chronic venous in-sufficiency. J Vasc Surg 1999; 30: 836–42.
17. Ramelet A-A, Boisseau MR, Allegra C et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: Current medical position, prospective views and final resolution. Clin Hemorheology Microcirculation 2005; 33: 309–19.
18. Bergan J, Scmid-Schonbein G, Coleridge-Smith Ph et al. Chronic Venous Disease. N Engl J Med 2006; 355: 488–98.
19. Шлякова А.А., Корнева К.Г., Кудыкин М.Н., Перетягин П.В. Особенности микроциркуляции нижних конечностей у пациентов с сахарным диабетом 2 типа в сочетании с хронической венозной недостаточностью. Терапевт. 2014; 1: 15–8. / Shliakova A.A., Korneva K.G., Kudykin M.N., Peretiagin P.V. Osobennosti mikrotsirkuliatsii nizhnikh konechnostei u patsientov s sakharnym diabetom 2 tipa v sochetanii s khronicheskoi venoznoi nedostatochnost'iu. Terapevt. 2014; 1: 15–8. [in Russian]
20. Schmid-Schonbein GW, Granger DN. Molecular Basis for Microcirculatory Disorders. Springer, 2003; p. 640.
21. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. Int Angiology 2008; 27: 1–59.
22. Ramelet A-A, Perrin M, Kern P, Bounameaux H. Phlebology, 5-th edition. Elsevier Masson, 2008; p. 565.
23. Davies AH. Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015. pii: S1078–5884(15)00699-1. doi: 10.1016/j.ejvs.2015.09.024
24. Varicose Veins in the Legs: The Diagnosis and Management of Varicose Veins. National Clinical Guideline Centre (UK). London: National Institute for Health and Care Excellence (UK), 2013.
25. Российские клинические рекомендации по диагностике и лечению хронических заболеваний вен. Утверждено совещанием экспертов 10.02.2013. Флебология. 2013; 2: 6–47. / Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu khronicheskikh zabolevanii ven. Utverzhdeno soveshchaniem ekspertov 10.02.2013. Flebologiia. 2013; 2: 6–47. [in Russian]
26. Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol 2005; 3 (1): 1–9. Review.
27. Jantet G. RELIEF Study Group. Chronic Venous Insufficiency: Worlwide Results of the RELIEF Study. Angiology 2002; 53: 245–56.
28. Rabe E, Agus GB, Roztocil K. Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial. Int Angiol 2015; 34 (5): 428–36. Epub 2015.
29. Pitsch F. Assessment of treatment efficacy on venous symptoms: the example of Detralex. Phlebolymphology 2008; 15: 137–42.
30. Belczak SQ, Sincos IR, Campos W et al. Veno-active drugs for chronic venous disease: A randomized, double-blind, placebo-controlled parallel-design trial. Phlebology 2014; 29 (7): 454–60. doi: 10.1177/0268355513489550. Epub 2013.
31. Colerige-Smith P, Lok C, Ramelet AA. Venous leg ulcer: meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg 2005; 30: 198–208.
________________________________________________
2. Jawien A, Grzela T, Ochwat A. Prevalence of chronic venous insufficiency in men and women in Poland: multicentre cross-sectional study in 40095 patients. Phlebology 2003; 81: 110–22.
3. Langer RD, Ho E, Deneberg JO et al. Relation-ship between symptoms and venous disease. Arch Int Med 2005; 165: 1420–4.
4. Labropoulos N, Stansby G. Venous and Lymphatic Diseases. Taylor & Francis, 2006; p. 559.
5. Eklof B, Perrin M, Konstantinos T. Delis et al. Up-date terminology of chronic venous disorders: The VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg 2009; 49: 498–501.
6. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. International Angiology 2008; 27: 1–59.
7. Bradbury A, Evans C, Allan P et al. What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ 1999; 318: 353–6.
8. Wrona M, Jöckel KH, Pannier F et al. Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. Eur J Vasc Endovasc Surg 2015; 50 (3): 360–7. doi: 10.1016/j.ejvs.2015.05.013. Epub 2015.
9. Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467.
10. Klement W, Arndt JO. Pain but no temperature sensation are evoked by termal stimulation of cutaneous veins in man. Neurosci Lett 1991; 123: 119–22.
11. Klement W, Arndt JO. Adenosine does not evoke pain from venous and paravascular nociceptors in the human. Cardivasc Res 1992; 26: 186–9.
12. Badier-Commandier C, Jacob MP, Michel JB. Le remodelage variqueux. Medecine Therapeutique 2006; 6: 718–23.
13. Boisseau MR. Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. Clin Hemorheol Microcirc 2007; 37 (3): 277–90. Review.
14. Danziger N. Pathophysiology of pain in venous disease. Phlebolymphology 2008; 15: 107–14.
15. Howlader MH, Smith PD. Symptoms of chronic venous disease and association with systemic inflammatory markers. J Vasc Surg 2003; 38: 950–4.
16. Padberg FT, Maniker AH, Carmel G et al. Sensory Impairment: a feature of chronic venous in-sufficiency. J Vasc Surg 1999; 30: 836–42.
17. Ramelet A-A, Boisseau MR, Allegra C et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: Current medical position, prospective views and final resolution. Clin Hemorheology Microcirculation 2005; 33: 309–19.
18. Bergan J, Scmid-Schonbein G, Coleridge-Smith Ph et al. Chronic Venous Disease. N Engl J Med 2006; 355: 488–98.
19. Shliakova A.A., Korneva K.G., Kudykin M.N., Peretiagin P.V. Osobennosti mikrotsirkuliatsii nizhnikh konechnostei u patsientov s sakharnym diabetom 2 tipa v sochetanii s khronicheskoi venoznoi nedostatochnost'iu. Terapevt. 2014; 1: 15–8. [in Russian]
20. Schmid-Schonbein GW, Granger DN. Molecular Basis for Microcirculatory Disorders. Springer, 2003; p. 640.
21. Nicolaides AN, Allegra C, Bergan J et al. Management of Chronic Venous Disorders of the Lower Limbs Guidelines According to Scientific Evidence. Int Angiology 2008; 27: 1–59.
22. Ramelet A-A, Perrin M, Kern P, Bounameaux H. Phlebology, 5-th edition. Elsevier Masson, 2008; p. 565.
23. Davies AH. Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015. pii: S1078–5884(15)00699-1. doi: 10.1016/j.ejvs.2015.09.024
24. Varicose Veins in the Legs: The Diagnosis and Management of Varicose Veins. National Clinical Guideline Centre (UK). London: National Institute for Health and Care Excellence (UK), 2013.
25. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu khronicheskikh zabolevanii ven. Utverzhdeno soveshchaniem ekspertov 10.02.2013. Flebologiia. 2013; 2: 6–47. [in Russian]
26. Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol 2005; 3 (1): 1–9. Review.
27. Jantet G. RELIEF Study Group. Chronic Venous Insufficiency: Worlwide Results of the RELIEF Study. Angiology 2002; 53: 245–56.
28. Rabe E, Agus GB, Roztocil K. Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial. Int Angiol 2015; 34 (5): 428–36. Epub 2015.
29. Pitsch F. Assessment of treatment efficacy on venous symptoms: the example of Detralex. Phlebolymphology 2008; 15: 137–42.
30. Belczak SQ, Sincos IR, Campos W et al. Veno-active drugs for chronic venous disease: A randomized, double-blind, placebo-controlled parallel-design trial. Phlebology 2014; 29 (7): 454–60. doi: 10.1177/0268355513489550. Epub 2013.
31. Colerige-Smith P, Lok C, Ramelet AA. Venous leg ulcer: meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg 2005; 30: 198–208.
Авторы
М.Н.Кудыкин*
ФГБУ Приволжский федеральный медицинский исследовательский центр Минздрава России. 603155, Россия, Нижний Новгород, Верхне-Волжская наб., д. 18
*mady5@yandex.ru
Nizhny Novgorod Research Institute of Traumatology and Orthopedics of Public of the Ministry of Health of the Russian Federation. 603155, Russian Federation, Nizhnii Novgorod, Verkhne-Volzhskaia nab., d. 18
*mady5@yandex.ru
ФГБУ Приволжский федеральный медицинский исследовательский центр Минздрава России. 603155, Россия, Нижний Новгород, Верхне-Волжская наб., д. 18
*mady5@yandex.ru
________________________________________________
Nizhny Novgorod Research Institute of Traumatology and Orthopedics of Public of the Ministry of Health of the Russian Federation. 603155, Russian Federation, Nizhnii Novgorod, Verkhne-Volzhskaia nab., d. 18
*mady5@yandex.ru
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