CC BY
26
МЕДИЧН1ПЕРСПЕКТИВИ / MEDICNIPERSPEKTIVI
UDC 616.321/.322-002-036.-085-053.2:615.281.9
https://doi.org/10.26641/2307-0404.2019.4.189264
T.A. Haiduk,
A.V. Cherhinets,
L.R. Shostakovych-Koretska
EFFECT OF ANTIBACTERIAL THERAPY ON THE CLINICAL COURSE OF STREPTOCOCCAL TONSILLOPHARYNGITIS IN CHILDREN
SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine» V. Vernadsky str., 9, Dnipro, 49044, Ukraine ДЗ «Днтропетровська медична академiя МОЗ Укра'ши» вул. Вернадського, 9, Днтро, 49044, Укра'ша e-mail: tamara.gayduk@gmail.com
Цитування: Медичт перспективы. 2019. Т. 24, № 4. С. 69-74 Cited: Medicniperspektivi. 2019;24(4):69-74
Key words: group A в-hemolytic streptococcus, tonsillopharyngitis, children, antibacterial therapy Ключовi слова: в-гемолтичний стрептокок групи А, тонзилофарингiт, dimu, aHmu6axmepiaMbHa тератя Ключевые слова: в-гемолитический стрептококк группы А, тонзиллофарингит, дети, антибактериальная терапия
Abstract. Effect of antibacterial therapy on the clinical course of streptococcal tonsillopharyngitis in children. Haiduk T., Cherhinets A., Shostakovych-Koretska L. The aim of this study was to determine the effect of antibiotic therapy (AT) on the clinical course of streptococcal tonsillopharyngitis (STP) in children, depending on the timing of its administration, since the data on the need to start AT in the first days of the disease to achieve the effect are controversial. A retrospective analysis of inpatient medical records at "The Communal Dnipro City Clinical Hospital N 21 named after Professor Ye.G. Popkova" DRC" in the period from January 2012 to December 2018 was conducted. The inclusion criteria for the study were: 1) the diagnosis - tonsillopharyngitis; 2) the age of the patient: 3 to 18 yrs; 3) the exclusion of an alternative diagnosis (diphtheria, infectious mononucleosis, scarlet fever); 4) no complications; 5) positive results of the culture study on в-hemolytic streptococcus group A (GAS) (Streptococcus pyogenes) of the oropharyngeal swab. The study included 109 medical cards of children with STP. Depending on the timing of the onset of rational AT, all patients were divided into 5 groups. The first one consisted of 27 children who received AT from the 1st day of the disease, 2nd - 48 children (AT from the 2nd day), 3rd - 17 children (AT from the 3rd day) and the fourth -7 children (ATfrom the 4th day), 5th - 10 children (ATfrom the 5th day). Clinical symptoms were evaluated by examining the patient with the main objective and subjective symptoms of STP. It was a retrospective open comparative study. All patients received the full recommended course of STP AT. The study showed no significant differences in the reduction of clinical symptoms of STP, regardless of the timing of antibiotic therapy (1-5 days from the onset of the disease) in almost half of patients with STP, which confirms the inadequacy of antibacterial therapy in children with tonsillopharyngitis. We believe that antibiotic therapy should only be used to prevent late complications in cases of children with tonsillopharyngitis only with a confirmed GAS etiology, and we propose the widespread use of the McIsaac Score, the Streptococcus Expression Test (RST) and the culture study of the oropharyngeal swab to confirm the etiology of GAS in children with tonsillopharyngitis to reduce the frequency of antibiotics overusing.
Реферат. Вплив aHT^aKTepiamHo'i терапп на клшчний nepe6ir стрептококового тонзилофаринпту в д^ей. Гайдук Т.А., Чергшець А.В., Шостакович-Корецька Л.Р. Метою цiеi роботи було визначити вплив анmибакmeрiальноi терапп (АТ) на клiнiчний пeрeбiг стрептококового mонзилофарингimу (СТФ) у дimeй залежно вiд meрмiнiв ii призначення, адже дат щодо нeобхiдносmi початку анmибакmeрiальноi терапп в пeршi днi хвороби для досягнення ефекту е суперечливими. Проведено ретроспективний аналiз медичних карт стацюнарного хворого на клШчнш базi КЗ «МКЛ №21 ш. професора С.Г. Попково'1» ДОР» м. Днтро в перюд iз счня 2016 по грудень 2018 року. Криmeрiями залучення до до^дження були: 1) дiагноз - тонзилофарингт; 2) вж пацiенmа вiд 3 до 18 роюв; 3) виключення альтернативного дiагнозу (дифmeрiя, iнфeкцiйний мононуклеоз, скарлатина); 4) вiдсуmнiсmь ускладнень; 5) позиmивнi результати культурального до^дження мазка з ротоглотки на в-гемолтичний стрептокок групи А (GAS) (Streptococcus pyogenes). До до^дження було залучено 109 медичних карт дтей, хворих на СТФ. Залежно вiд meрмiнiв початку рацiональноi АТ уах пацiенmiв було розподшено на 5 груп. Першу склали 27 дimeй, як отримували АТ з 1-i доби захворювання, 2-у -48 дimeй (АТз 2-i доби), 3-ю - 17 дimeй (АТз 3-i доби) та четверту- 7 дтей (АТз 4-i доби), 5-ту - 10 дimeй (АТ з 5-i доби). Оцтка клiнiчноi симптоматики здтснювалась при оглядi пацiенmа за основними об 'ективними та суб'ективними симптомами СТФ. Це було ретроспективне вiдкриme порiвняльнe до^дження. Уа пащенти отримали повний рекомендований курс АТ СТФ. Проведене до^дження показало вiдсуmнiсmь значущих
19/ Том XXIV/ 4
69
вгдмтностей у зменшеннi клтчних симптомгв СТФ незалежно eid термгнгв призначення антибактер1ально1 терапИ (на 1-5 дш eid початку захворювання) майже в половини пацieнтiв 3i СТФ. Таким чином, нашi дат спiвпадають з бшьш рантми до^дженнями, в яких повiдомляeться, що антибактерiальна тератя мае незначний вплив на клтчний перебш СТФ у дтей i мае за мету, передуем, профтактику ускладнень. Ми вважаемо, що антибiотикотерапiя мае призначатися тшьки для запобiгання тзнш ускладненням у випадках тонзилофарингту в дiтей лише з пiдтвердженою етiологieю GAS, i пропонуемо широке застосування шкали Mclsaac, експрес-тесту на стрептокок (RST) та бактерiологiчне до^дження мазка з ротоглотки для пiдтвердження етiологii GAS у дтей з тонзилофарингтом з метою зниження частоти надмiрного використання антибiотикiв.
Group A p-hemolytic streptococcus (GAS) is one of the most common pathogens that infects children and adolescents with a wide variety of clinical manifestations, from relatively benign tonsillo-pharyngitis to invasive forms of GAS infection, life-threatening for infants [1, 5, 11]. Moreover, postponed GAS tonsillopharyngitis can cause severe complications in the form of acute rheumatic fever, post-streptococcal glomerulonephritis, and childhood autoimmune neuropsychiatric disorder (PANDAS) [1, 9, 10].
The relevance of the study of tonsillopharyngitis in children caused by GAS is due, to among other things, the high incidence of the disease in children aged 5-15 years - 9 to 12 cases of GAS tonsillopharyngitis per 100 patient-years [2]. Among all cases of pharyngitis in children, GAS etiology of tonsillopharyngitis is detected in 30-40% [10, 12].
Sore throat is one of the most common reasons for prescribing antibiotics in children and adults [13]. The aim of the antibacterial therapy of acute streptococcal tonsillopharyngitis is primarily the eradication of GAS, which leads not only to the reduction of symptoms and duration of the disease, but also to the prevention of the spread of infection, early and late complications associated with GAS [9, 11, 12, 13]. However, there are studies showing that antibiotics administration in the early days of the disease is not rational, since not always the etiology of tonsillopharyngitis is GAS, which causes purulent complications, acute rheumatic fever, poststreptococcal glomerulonephritis (PSGN), and others [7].
However, antibiotics are most effective when positive results are obtained from the oral oropha-ryngeal smear for GAS [4, 13].
There are studies that show a small effect of AT on pharyngitis with possible GAS etiology in the primary clinical evaluation of acute symptoms. At the same time, they showed that the onset of AT up to 10th day after the onset of symptoms effectively prevents the development of most complications (acute rheumatic fever, poststreptococcal glomerulonephritis, PANDAS), and the early administration of antibiotics before the confirmation of GAS etiology of tonsillopharyngitis, rarely is of urgent importance [6].
At the same time, some studies demonstrate a decrease in the duration of streptococcal tonsillopharyngitis (STP) symptoms on average by 16 hours in AT of STP [13].
The aim of this study was to determine AT effect on the STP clinical course in children depending on the timing of its administration.
MATERIALS AND METHODS OF RESEARCH A retrospective analysis of inpatient medical records at "Communal Dnipro City Clinical Hospital N 21 named after Professor Ye.G. Popkova" of Dni-propetrovsk Regional Council" in the period from January 2012 to December 2018 was conducted. The inclusion criteria for the study were: 1) diagnosis -tonsillopharyngitis; 2) age of the patient from 3 to 18 years; 3) elimination of alternative diagnosis (diphtheria, infectious mononucleosis, scarlet fever); 4) lack of complications (paratonsillar abscess, acute otitis media, sinusitis, mastoiditis, purulent cervical lymphadenitis requiring surgical treatment, burn of the oropharynx); 5) positive results of GAS (Streptococcus pyogenes) culture study of a swab from the oropharynx.
Definitions of antibacterial therapy of STP In the study we used the concept of rational (according to clinical guidelines) and irrational use of antibiotics for STP treatment [3, 4, 13]. By rational AT we mean that the patient received any antibacterial agents systemically from the group of P-lactams, macrolides, linkosamides. By irrational AT we mean that the patient was treated systemi-cally with antibiotics of the aminoglycoside group, trimethoprim / sulfamethoxazole, or exclusively with topical antibiotics and antiseptics, or with traditional medicine methods and homeopathic preparations monotherapy.
Characteristics of the contingent of the study According to the above criteria, the study included 109 medical cards of children with STP. Depending on the timing of a rational AT starting, all patients were divided into 5 groups. The first one consisted of 27 children who received AT from the 1st day of the disease, 2nd - 48 children (AT from the 2nd day), 3rd - 17 children (AT from the 3rd day) and the fourth - 7 children (AT from the 4th
MEffHHHI nEPCnEKTHBH / MEDICNIPERSPEKTIVI
day), 5th - 10 children (AT from the 5th day). Characteristics of groups are given in Table 1.
As an add-on therapy, all patients received antipyretics as needed (paracetamol, ibuprofen, metamizole). Evaluation of STP clinical symptomatology The clinical symptomatology was evaluated at the patients' examination by the main objective (fever, hyperemia and edema of the tonsils, layers on the tonsils, tonsillar lymph nodes enlargement) and subjective (sore throat, pain in tonsillar lymph nodes) symptoms of STP. Each symptom was evaluated as either positive (positive) or absent (negative).
Research design
This is a retrospective open comparative study. Comparison of evaluation data of STP clinical symptomatology between groups was carried out on the 2nd day from the onset of the disease between the 1st and 2nd groups, on the 3rd day - between the 1st, 2nd and 3rd groups, on the 4th day - between the 1st, 2nd, 3rd and 4th groups, as well as on the 5th and 10th days among all the experimental groups.
Statistical analysis
Comparison of the indicators between the groups was performed using the corrected Yeats method (x2). The results were considered reliable at p<0.05.
Table 1
Characteristics of study groups
Indicator Groups
1-st 2-nd 3-rd 4-th 5-th
Number, n 27 48 17 7 10
Age, years
Interval 5-18 4-17 4-18 4-13 4-12
M±m 12,4±3,8 11,3±4,0 11,7±3,6 6,6±2,1 6,4±2,1
95% CI 10,8-14,2 10,2-12,5 9,8-13,7 4,1-9,9 4,0-9,5
Sex: m, n (%) / f, n 13(48,1)/14 29(60,4)/19 10(58,8)/7 4(57,1)/3 6(60)/4
Rational AT, n (%)
Penicillins 3(11,1) 7 (14,6) 2 (11,8) 0 0
Aminopenicillins 3 (11,1) 4 (8,3) 3 (17,7) 3 (42,9) 5 (50)
Cephalosporins 17 (63,0) 30 (62,5) 9 (52,9) 3 (42,9) 1 (10)
Macrolides 4 (14,8) 7 (14,6) 2 (11,8) 1 (14,2) 4 (40)
Lincosamides 0 0 1 (5,8) 0 0
RESULTS AND DISCUSSION
All 109 patients completed the study and received the full recommended AT (from 5 to 10 days depending on the pharmacology group of a drug) of STP course.
The results of a comparative analysis of STP clinical symptoms evaluation between the 1st, 2nd, and 3rd groups on the 2nd and 3rd days from the start of rational AT showed that 100% of cases (92 patients) had all 6 symptoms that were evaluated.
In addition, there were no probable differences in the frequency of STP clinical manifestations bet-
ween the groups, depending on the timing of the beginning of rational AT of STP both on the 4th and 5th day of the disease (Table 2, 3).
Moreover, on the 4th day from the onset of the disease, the fever, patch on the tonsils, sore throat and tenderness of the tonsillar lymph nodes remained almost in '/2 patients in all comparison groups regardless of AT timing. Hyperemia and edema of the tonsils, increased tonsillar lymph nodes were present in all patients with STP.
19/ TOM XXIV/ 4
71
Table 2
Comparison of STP clinical manifestations under the influence of rational AT, depending on the date of its beginning, on the 4th day of the disease
Symptom Group Probability of difference
1-st 2-nd 3-rd 4-th
Fever, n (%) 12 (44,4) 28 (58,3) 7 (41,2) 4 (57,1) X2=2,88; К=3; p<0,3
Hyperemia and swelling of the tonsils, n (%) 27 (100) 48 (100) 17 (100) 7 (100) N
Patch on the tonsils, n (%) 18 (66,6) 27 (56,3) 10 (58,8) 4 (57,1) X2=0,58; К=3; p<0,5
Enlargement of tonsillar lymph nodes, n (%) 27 (100) 48 (100) 17 (100) 7 (100) N
Sore throat, n (%) 12 (44,4) 21 (43,8) 9 (52,9) 4 (57,1) X2=1,0; К=3; p<0,4
Morbid tonsillar lymph nodes, n (%) 8 (29,6) 25 (52,1) 7 (41,2) 2 (28,6) X2=4,2; К=3; p<0,2
Note. N - not subject to statistical processing due to the lack of difference (100% have a sign).
However, significant reduction or absence of We did not find any cases of complications of
these symptoms (fever, patches on the tonsils, sore STP in the form of paratonsillar abscess, acute otitis
throat and soreness of tonsillar lymph nodes) was media, sinusitis, mastoiditis, purulent cervical
noted in all patients in comparative groups on the lymphadenitis which would require surgical treat-
5th day from the onset of the disease. ment throughout the observation period.
Table 3
Comparison of STP clinical manifestations under the influence of rational AT, depending on the date of its beginning, on the 5th day of the disease
Symptom Group Probability of difference
1-st 2-nd 3-rd 4-th 5-th
Fever, n (%) 2 (7,4) 6 (12,5) 1 (5,9) 1 (14,3) 1 (10) X2=2,6; К=4; p<0,4
Hyperemia and swelling of the tonsils, n (%) 27 (100) 48 (100) 17 (100) 7 (100) 10 (100) N
Patch on the tonsils, n (%) 1 (3,7) 3 (6,3) 1 (5,9) 1 (14,2) 1 (10) X2=1,37; К=4; p<0,4
Enlargement of tonsillar lymph nodes, n (%) 27(100) 48 (100) 17 (100) 7 (100) 10 (100) N
Sore throat, n (%) 0 1 (2) 1 (5,8) 0 0 X2=0,002; К=4; p<0,5
Morbid tonsillar lymph nodes, n (%) 0 1 (2) 0 0 0 X2=0,001: К=4; p<0,5
Note. N - not subject to statistical processing due to the lack of difference (100% have a sign).
The study showed no significant differences in the reduction of clinical symptoms of STP, regardless of the timing of the antibiotic therapy administration (1-5 days from the onset of the disease) in almost half of patients with STP. The obtained data are consistent with the results of the Cochrane systematic review of the antibiotics administration in tonsillopharyngitis (27 studies, of which only 3 were conducted exclusively in children). It has been shown that sore throat and
fever have reduced in the course of antibiotic treatment in only half of patients with STP. Moreover, in one week in about 90% of patients treated and those who did not receive the etiotropic drug, the symptoms were no longer present [3, 7].
CONCLUSION
Thus, our research data support previous studies that the antibacterial therapy has a little if any effect on the clinical course of streptococcal tonsil-lopharyngitis in children. We consider antibiotics
МЕДИЧН1ПЕРСПЕКТИВИ / MEDICNIPERSPEKTIVI
therapy to be prescribed just for prevention of the late complications in cases of tonsillopharyngitis in pediatric patients with confirmed GAS etiology only. We offer extensive applying of the Mclsaac score [8], RST, and a culture smear to confirm the
etiology of GAS in children with tonsillopharyngitis in order to reduce the incidence of antibiotics overusing.
Conflict of interest. Authors declare no conflicts of interest.
REFERENCES
1. Nishiyama M, Morioka I, Taniguchi-Ikeda M, Mori T, Tomioka K, Nakanishi K, Fujimura J, Nishimu-ra N, Nozu K, Nagase H, Ishibashi K, Ishida A, Iijima K. Clinical features predicting group A streptococcal pharyngitis in a Japanese paediatric primary emergency medical centre. J Int Med Res. 2018 May;46(5):1791-800. Epub 2018 Mar 8. PubMed PMID: 29517940; PubMed Central PMCID: PMC5991234. doi: https://doi.org/10.1177/0300060517752954
2. Danchin MH, Rogers S, Kelpie L, et al. Burden of acute sore throat and group A streptococcal pharyngitis in school-aged children and their families in Australia. Pediatrics Nov. 2007;120(5):950-7. doi: https://doi.org/10.1542/peds.2006-3368
3. van Driel ML, De Sutter AI, Habraken H, Thor-ning S, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev. 2016 Sep 11;9(9):CD004406. PubMed PMID: 27614728; PubMed Central PMCID: PMC6457741. doi: https://doi.org/10.1002/14651858.CD004406.pub4
4. Ellis CS, Camacho-Walsh ME. AGREE Appraisal of Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis. Advanced Emergency Nursing Journal. 2015;37(1):34-41. doi: https://doi.org/10.1097/TME.0000000000000044
5. Gottlieb M, Koyfman A, Long B. Clinical Mimics: An Emergency Medicine-Focused Review of Streptococcal Pharyngitis Mimics. J Emerg Med. 2018 May;54(5):619-29. doi: https://doi.org/10.1016/jjemermed.2018.01.031
6. Khan ZZ, Salvaggio MR. Group A Streptococcal (GAS) Infections. Medscape. [updated 2018 Sep. 07] Available from: https://emedicine.medscape.com/article/-228936-overview#showall
7. Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child. 2008 Jun;93(6):474-8. doi: https://doi.org/10.1136/adc.2006.113506
8. McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998 Jan 13;158(1):75-83. PubMed PMID: 9475915; PubMed Central PMCID: PMC1228750.
9. Martin WJ, Steer AC, Smeesters PR, et al. Postinfectious group A streptococcal autoimmune syndromes and the heart. Autoimmun Rev. 2015 Aug;14(8):710-25. doi: https://doi.org/10.1016Zj.autrev.2015.04.005
10. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis. Circulation. 2009 Mar 24;119(11):1541-51.
doi: doi.org/10.1161/CIRCULATI0NAHA.109.191959
11. Rammelkamp CH, Wannamaker LW, Denny FW. The Epidemiology and Prevention of Rheumatic Fever. Bull N Y Acad Med. 1952 May;28(5):321-34. PubMed PMID: 19312604; PubMed Central PMCID: PMC1877185.
12. Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics. 2010 Sep;126(3):e557-64. doi: https://doi.org/10.1542/peds.2009-2648
13. Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2013 Nov 5;(11):CD000023.
doi: https://doi.org/10.1002/14651858.CD000023.pub4
СПИСОК Л1ТЕРАТУРИ
1. Clinical features predicting group A streptococcal pharyngitis in a Japanese paediatric primary emergency medical centre / M. Nishiyama et al. J. Int. Med. Res. 2018. Vol. 46, No. 5. P. 17911800. DOI: https://doi.org/10.1177/0300060517752954
2. Danchin M., Kelpie L., Rogers S. Burden of acute sore throat and group A streptococcal pharyngitis in school-aged children and their families in Australia. Pediatrics. 2007. Vol. 120. P. 950-957. DOI: https://doi.org/10.1542/peds.2006-3368
3. Different antibiotic treatments for group A streptococcal pharyngitis / M. L. van Driel et al. Cochrane Database Syst Rev. 2016. Vol. 9, No. 9. P. CD004406.
Published 2016 Sep 11.
DOI: https:// doi:10.1002/14651858.CD004406.pub4
4. Ellis C. S., Camacho-Walsh M. E. AGREE Appraisal of Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis.
Advanced Emergency Nursing Journal. 2015. Vol. 37, No. 1. P. 34-41.
DOI: https://doi.org/10.1097/TME.0000000000000044
5. Gottlieb M., Long B., Koyfman A. Clinical Mimics: An Emergency Medicine-Focused Review of Strep-tococcal Pharyngitis Mimics. J. Emerg. Med. 2018. Vol. 54, No. 5. P. 619-629
DOI: https://doi.org/10.1016/jjemermed.2018.01.031
19/ Том XXV/ 4
73
6. Khan Z. Z., Salvaggio M. R. Group A Streptococcal (GAS) Infections. Medscape [updated 2018 Sep 07]. URL: https://emedicine.medscape.com/article/228936-overview#showall
7. Lennon D. R., Farrell E., Martin D. R., Stewart J. M. Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child. 2008. Jun. (Vol. 93, No. 6). P. 474-478. DOI: https://doi.org/10.1136/adc.2006.113506
8. Mclsaac W. J., White D., Tannenbaum D., Low D. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998. Vol. 158, No. 1. P. 75-83.
9. Post-infectious group A streptococcal autoimmune syndromes and the heart / W. J. Martin et al. Autoimmun Rev. 2015. Aug. (Vol. 14, No. 8), P. 710-725. DOI: https://doi.org/10.1016/j.autrev.2015.04.005
10. Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis / M. A. Ger-
ber et al. Circulation. 2009. Mar. 24. (Vol. 119, No. 11). P. 1541-1551.
DOI: doi.org/10.1161/CIRCULATI0NAHA.109.191959
11. Rammelkamp C. H., Wannamaker L. W., Denny F. W. The Epidemiology and Prevention of Rheumatic Fever. Bull N Y Acad Med. 1952. May. (Vol. 28, No. 5). P. 321-334. PubMed PMID: 19312604; PubMed Central PMCID: PMC1877185.
12. Shaikh N., Leonard E., Martin J. M. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics. 2010. Sep. (Vol. 126, No. 3). P. 557-64.
DOI: https://doi.org/10.1542/peds.2009-2648
13. Spinks A., Glasziou P. P., Del Mar C. B. Antibiotics for sore throat. Cochrane Database Syst Rev. 2013. Nov. (Vol. 5, No. 11). P. CD000023. DOI: https://doi.org/10.1002/14651858.CD000023.pub4
Crana Hagmm^a go pegaKmi' 28.06.2019
♦
UDC 616.13-004. 6-039. 35:616.831-005.4-06 https://doi.Org/10.26641/2307-0404.2019.4.189299
L.A. Dzyak1, 2 COMORBIDITY PROFILE IN CHRONIC
О А Rosytska 2 BRAIN ISCHEMIA ON THE BACKGROUND
OF MULTIFOCAL ATHEROSCLEROSIS
SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Nervous Diseases and Neurosurgery FPE1
Department of Family Medicine FPE 2
V. Vernadsky str., 9, Dnipro, 49044, Ukraine
ДЗ «Днтропетровська медична академiя МОЗ Укра'ни»
кафедра нервових хвороб та нейрохiрургii ФПО 1
(зав. - член.-кор. НАМН Укра'ши, д. мед. н., проф. Л.А. Дзяк)
кафедра амейно' медицини ФПО 2
(зав. - д. мед. н., доц. 1.Л. Височина)
вул. В. Вернадського, 9, Днтро, 49044, Укра'на
e-mail: aleksa2005@ua.fm
Цитування: Медичт перспективы. 2019. Т. 24, № 4. С. 74-83 Cited: Medicniperspektivi. 2019;24(4):74-83
Key words: chronic brain ischemia, risk factors, comorbidity, Charlson's comorbidity index modified Ключовi слова: хронiчна iшeмiя мозку, фактори ризику, коморбiднiсmь, тдекс коморбiдносmi Charlson модифiкований
Ключевые слова: хроническая ишемия мозга, факторы риска, коморбидность, индекс коморбидности Charlson модифицированный
