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Crana Hagmm^a go pegaKmi' 28.06.2019
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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: хротчна iшемiя мозку, фактори ризику, K0M0p6idnicmb, тдекс K0M0p6idH0cmi Charlson модифiкований
Ключевые слова: хроническая ишемия мозга, факторы риска, коморбидность, индекс коморбидности Charlson модифицированный
Abstract. Comorbidity profile in chronic brain ischemia on the background of multifocal atherosclerosis. Dzyak L.A., Rosytska О.А. Aim to evaluate the comorbidity profile in patients with chronic cerebral ischemia on the background of multifocal atherosclerosis. The study included 137 patients aged 40 to 84 years with chronic cerebral ischemia (CCI) on the background of multifocal atherosclerosis, which were divided into three clinical groups depending on the localization of vascular lesions by stenosing atherosclerosis. The co-morbidity profile and severity were evaluated using the Charlson's index in modification of R.A. Deyo (1992). In CCI patients, regardless of the combination of vascular basins affected by atherosclerosis, a severe degree of comorbidity prevailed - the Charlson's comorbidity index (IC) was predominantly > 5points (84.7% of cases). In the analysis of IC in age categories, depending on the combination of atherosclerotic lesions of the vascular basins, it was found that comorbidity of severe degree (IC> 5) was predominantly represented by patients of the older age group (60-74 years), and comorbidity of moderate severity (IC<5) - patients of middle age group (45-59 years). A median difference of 3 points in assessing the mean value of age-matched comorbidity index showed that age, as a non-modifiable risk factor, in 1/3 cases determines the comorbidity index, which depends on the number of vascular basins affected by atherosclerosis. In 2/3 of the cases it is a modified comorbid pathology. Assessment of IC in clinical groups, taking into account the nature of the disease course (p <0.05), showed a correlation between the number of atherosclerosis affected by vascular basins, the severity of the clinical course of CCI and the severity of comorbidity. The severity of comorbidity, as measured by the Charlson's index modified by R.A. Deyo, depends on age and determines the nature of the atherosclerotic lesion, as well as the severity of the clinical course of CCI. Assessing the profile and severity of comorbidity makes it possible to influence the nature of the development and course of brain ischemia, which is caused by systemic atherosclerotic lesions of the vascular system.
Реферат. Профшь коморбщност при хрошчнш шеми мозку на фош мультифокального атеросклерозу. Дзяк Л.А., Росицька О.А. Мета до^дження - оцтити профшь K0M0p6idH0cmi у хворих з хротчною iшемieю мозку на тлi мультифокального атеросклерозу. У до^дження включено 137 хворих у вщ eid 40 до 84 ротв з хротчною iшемieю мозку (Х1М) на тлi мультифокального атеросклерозу, як були розподiленi на три клiнiчнi групи залежно вiд локал1зацИ ураження судинних басейтв стенозуючим атеросклерозом. Проводилась оцiнка профтю коморбiдностi i ступеня ii тяжкостi за допомогою тдексу Charlson у модифкацП R.A. Deyo (1992 г.). У хворих з Х1М незалежно вiд поеднання уражених атеросклерозом судинних басейнiв переважав тяжкий ступiнь коморбiдностi - тдекс коморбiдностi (IK) Charlson становив переважно> 5 балiв (84,7% випадтв). При аналiзi IK у вiкових категорiях залежно вiд поеднання атеросклеротичного ураження судинних басейтв встановлено, що коморбiднiсть тяжкого ступеня (IK> 5) була представлена переважно особами старшо'1' вiковоi групи (60-74 роки), а коморбiднiсть середнього ступеня тяжкостi (IK <5) - особами середньо'1' вково'1' групи (45-59 роюв). Пзниця медiани на 3 бали при оцiнцi середнього значення тдексу коморбiдностi з урахуванням вк показала, що вж, як фактор ризику, що не модиф^еться, в 1/3 випадтв визначае тдекс коморбiдностi, який залежить вiд кiлькостi судинних басейнiв, уражених атеросклерозом. У 2/3 же випадюв -це коморбiдна патологiя, яка модиф^еться. Оцiнка IK у клтчних групах з урахуванням характеру перебшу захворювання достовiрно (p <0,05) показала залежнкть мiж юльюстю уражених атеросклерозом судинних басейнiв, тяжюстю клтчного перебiгу ХИМ i ступенем тяжкостi коморбiдностi. Cтупiнь тяжкостi коморбiдностi, що оцтюеться за тдексом Charlson у модифжацп R.A. Deyo, залежить вiд вк i визначае характер атеросклеротичного ураження, а також тяюсть клтчного перебшу ХИМ. Оцтка профшю та тяжкостi коморбiдностi дае можливкть впливати на характер розвитку i переб^ шеми мозку, яка зумовлена системним атеросклеротичним ураженням судинно'1' системи.
The number of patients suffering from several diseases increases every year [1]. Comorbidity is the coexistence of two and / or more syndromes or diseases in one patient, pathogenetically interacting with each other or coinciding in time. Both conditions are the result of a single pathological process, and the differences in their course are due to the influence of external behavioral factors [3].
Comorbidity not only acts as a global medical problem and determines an individual prognosis for each patient (functionality, duration and quality of life, disability and mortality), but also has large-scale social consequences at the population level. Especially it affects the determination of the diagnostic and therapeutic approach for patient
management [4]. Often, it is comorbid lesions that worsen the course of the underlying disease and / or lead to chronicity, cause disability and premature death of the working population. The presence of comorbid diseases significantly worsens the course of each disease separately [1]
Most patients, especially the elderly and senile, have a combined pathology: damage to the brain, cardiovascular system and kidneys, as well as metabolic syndrome. On average, examination of elderly and senile patients reveals from 4 to 8 leading diseases. With age, there is an increase in the number of patients with coronary heart disease, arterial hypertension (and their complications -myocardial infarction and heart failure), chronic
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kidney disease, diabetes mellitus (and its complications - primarily diabetic nephropathy, retinopathy and polyneuropathy), anemic syndrome. Each of the diseases is an independent risk factor for death in elderly patients. It has been established that risk factors for cerebrovascular diseases are simultaneously risk factors for cardiovascular diseases. The development and progression of cerebrovascular diseases, as well as cardiovascular diseases, is closely associated with modifiable risk factors (smoking, unhealthy diet, physical inactivity, psychosocial factors, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, microalbuminuria, hyperhomocysteinemia, endothelial dysfunction and other factors (age, gender, adverse heredity) [5].
It was found that multidimensional indices, including the degree of severity (measured by functional constraint) for assessing comorbidity, correlate well with health outcomes, including quality of life and mortality. However, there are much fewer studies evaluating the severity or functional limitation of comorbidity [9, 11. For example, comorbidity prevents rehabilitation after a stroke [10], increases the number of complications after surgery, and increases the likelihood of falls in the elderly. Thus, the effect of comorbidity on the clinical manifestations, diagnosis, prognosis and treatment of many diseases is multifaceted and individual [2]. High comorbidity is an independent predictor of poor prognosis for survival [8] and can lead to mortality not associated with the underlying disease [11].
The possibility of the development and progression of cerebrovascular diseases, including chronic cerebral ischemia, increases with an increase in the number of compatibility and severity of behavioral factors and comorbid conditions. Comorbidity and potentially interacting vascular risk factors associated with the prevalence of atherosclerosis, which determine its heterogeneity, occupy an important place in the study of chronic brain ischemia. In domestic literature, such studies are not adequately covered, which determines the relevance of this work.
The purpose of the study: to evaluate the profile of comorbidity in patients with chronic brain ischemia on the background of multifocal atherosclerosis.
MATERIALS AND METHODS OF RESEARCH
The study included 137 patients aged 40 to 84 years, with multifocal vascular lesions. Of these, 107 (78.1%) patients are male and 30 (21.9%) are female. The average age of patients was (63.6±0,8) years.
Depending on the location of the lesion of vascular beds with stenosing atherosclerosis, all patients were divided into three clinical groups: I group - 30 (21.9%) patients with vascular lesions of the brain, heart and lower extremities; II group - 87
(63.5%) patients with vascular lesions of the brain and heart; III group - 20 (14.6%) patients with vascular lesions of the brain and lower extremities. The distribution of patients depending on the course of chronic cerebral ischemia (CCI) were as follows: CCI no episodes of acute ischemia of the disease in anamnesis (23 patients), CCI with TIA in anamnesis (15 patients), CCI with a single cerebral infarction in the anamnesis (59 patients), with repeated infarcts of the brain in history (40 patients).
Neurological status was assessed with the identification of leading clinical symptoms and the establishment of a form of cerebral circulation disorder. The nature of vascular lesions was refined by ultrasound Doppler ultrasound of the extra- and intracranial arteries on the device HP SONOS-1000 HP made by Hewlett Packard (USA), as well as selective cerebral angiography (according to indications). Structural lesions and their extent were determined using a brain MRI on the apparatus of "General Electric" (USA).
Assessment of the comorbidity profile was performed using the Charlson's index in the modification of R.A. Deyo (1992) [10,11], which is a point system for estimating age, presence and number of comorbid diseases and allows to determine the severity of comorbidity: moderate - Charlson's comorbidity index <5 and severe - Charlson's 5 comorbidity index (Table 1).
Statistical analysis of the obtained data was performed using the licensed program Statis-tica v.6.1® (StatSoft, USA) (serial number AGAR909E415822FA). Mean values are presented as arithmetic mean with standard error (M±m) in cases of normal distribution law (Shapiro-Wilk test) or as median and quartile - Me (25-75%) in other cases. When comparing the relative indicators Fisher's two-way exact test (FTWET), was used for medium - the Mann-Whitney test.
RESULTS AND DISCUSSIONS
The analysis of the comorbid profile of patients with CCI in clinical groups showed heterogeneity of risk factors and concomitant diseases that contribute to the development and progression of vascular damage to the brain (Table 2).
It was found that hypertension in 92.7% of cases and ischemic heart disease in 85.4% of cases predo-minanted among pathogenetically related comorbid diseases. In 22.6% of cases, patients with gastrointestinal tract pathology were identified, which we attributed to pathogenetically unrelated comorbid diseases. However, the term "pathogenetically unrelated diseases" is very conditional, given the concept of uniform behavioral factors that can lead to the development of atherosclerotic lesions of the
vascular system and ischemic events. In the presented study, among the behavioral modifiable risk factors, the leading ones were identified: eating
disorders (94.9%), physical inactivity (63.5%) and smoking (57.7%), and an unmodifiable factor - age (60 years and older - 66.4%)
Table 1
The presence of comorbid pathology and its score in the calculation of the Charlson comorbidity index in the modification of R.A. Deyo
Disease
Points
Myocardial infarction 1
Angina / heart failure 1
Hypertension 1
Peripheral artery disease 1
CVD or transient cerebral circulation disorders 1
Disorders of cerebral circulation with hemiplegia 2
Chronic lung diseases 1
Diabetes 1
Targeted diabetes mellitus 2
Moderate or severe kidney damage 2
Moderate liver damage 2
Severe liver damage 3
Disease of thyroid gland 1
Connective tissue disease 1
Gastric ulcer 1
Dementia 1
Tumor without metastases (lymphoma, leukemia) 2
Depression 1
Skin cancer 2
Malignant tumors with metastases 6
AIDS (disease) 6
+ 1 point added for every 10 years of life after 40
Considering the large number of combinations of luated the severity of comorbidity in selected clinical comorbid diseases in patients with CCI, we eva- groups (Table 3).
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Table 2
The prevalence of comorbid conditions and risk factors in patients with CCI in clinical groups
Number of patients examined
Comorbid conditions and risk factors I group (n=30) II group (n=87) Ill group (n=20) Total in the general group (n=137)
n % n % n % n %
1. Pathogenetically related
Hypertension 28 93.3 81 93.1 18 90 127 96.7
IHD, including 30 100 рш 87 100 рш - рщ 117 85.4
- IM 10 33.3 рш 18 20.7 рш - PI,П 28 20.4
Diabetes mellitus 13 43.3 рп 12 13.8 рцп 8 40 рп 33 24.1
Coronary artery disease (CAD) 28 93.3 рп - рцп 18 90 рп 46 33.6
2. Pathogenetically unrelated
Diseases of the pulmonary system 6 20 8 9.2 - - 14 10.2
Disease of thyroid gland 5 16.7 5 5.7 - - 10 7.3
Gastrointestinal diseases 8 26.7 16 18.4 7 35 31 22.6
Diseases of the urogenital system 9 30 рп,Ш 10 11.5 р! - PI 19 13.9
3. Vascular risk factors
Smoking 17 56.7 49 56.3 13 65 79 57.7
Eating disorders 29 96.6 83 95.4 18 90 130 94.9
Hypodynamia 25 83.3 рп 49 56.3 PI 13 65 87 63.5
Chronic stress 15 50 33 37.9 рш 14 70 рп 62 45.2
Alcohol abuse 4 13.3 9 10.3 3 15 16 11.7
Age.years
25-44 - - 2 2.3 - - 2 1.5
45-59 5 16.7 рш 30 34.5 9 45 PI 44 32.1
60-74 19 63.3 48 55.2 8 40 75 54.7
75-90 6 20 7 8.0 3 15 16 11.7
Note. pi, pll, pill - p< 0,05 compared to the corresponding group I, II, III according to Fisher test.
Table 3
Characteristics of the degree of comorbidity in patients with CCI in clinical groups
Number of examined patients
The degree of severity of comorbidity I group (n=30) II group (n=87) Ill (n group =20) Total in the general group (n=137)
n % n % n % n %
Moderate degree of comorbidity (CI <5) - Pii,iii 17 19.5 Pi 4 20 Pi 21 15.3
Severe degree of comorbidity (CI > 5) 30 100 Pii,iii 70 80.5 Pi 16 80 PI 116 84.7
Note. pi, pll, pill - p< 0,05 compared to the corresponding group I, II, III according to Fisher test.
The analysis of the comorbidity profile in the selected clinical groups showed the heterogeneity of its severity associated with number of vascular basins affected by atherosclerosis. It was found that in patients with CCI, regardless of the combination of vascular beds affected by atherosclerosis, a severe degree of comorbidity prevailed - Charlson's comorbidity index (CI) was predominantly> 5 points (84.7% of cases). Thus, if in the first clinical group with combined atherosclerotic lesions of the vessels of the brain, heart and lower extremities, a severe degree of comorbidity was observed in 100% of cases, then in the II and III groups it was 80.5% and 80.0%, respectively (p<0.05 compared with group I), and a moderate degree of comorbidity in these groups was 19.5% and 20.0% of cases, respectively.
It was found that the severity of comorbidity, which means an increase in the number of comorbid conditions, affects not only the number of vascular basins affected by atherosclerosis, but also the nature
(severity) of clinical manifestations of vascular brain lesions in patients with CCI (Table 4). Thus, if patients with a history of TIA had a severe degree of comorbidity - 66.7% of cases, then in patients with a history of stroke, it was already 79.7% of cases, and in patients with a history of relapses - 90% of cases.
To clarify the factors that determine the severity of comorbidity in clinical groups the comorbidity index was evaluated, taking into account age categories (Table 5).
In the analysis of the comorbidity index (IC) in age categories in selected clinical groups depending on a combination of the atherosclerotic lesion of the vascular beds it was established that severe comorbidity (IC>5) was represented mainly by the older age group (60-74 years) and comorbidity of moderate severity (IC<5) - middle-age group (45-59 years). In individuals aged over 75 years only severe comor-bidity was established (IC>5).
Table 4
Characteristics of the degree of comorbidity severity in patients with CCI, taking into account the nature of the disease
Number of examined patients
The degree of severity of comorbidity CCI without Acute Brain Disorders (n=23) (1) CCI with TIA (n=15) (2) CCI with ischemic stroke (3) (n=59) CCI with recurrent stroke (1) (n=40) Total in the general group (n=137)
n % n % n % n % n %
Moderate degree of comorbidity (CI <5) - P2,3 5 33.3 P1 12 20.3 P1 4 10.0 21 15.3
Severe degree of comorbidity (CI > 5) 23 100 P2,3 10 66.7 P1 47 79.7 P1 36 90.0 116 84.7
Note. p1, p2, p3, p4 - p< 0,05 compared to the corresponding group I, II, III, IV according to Fisher test.
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Table 5
Characteristics of the comorbidity index in clinical groups by age
Number of examined patients
The degree of severity of comorbidity I group (n=30) II group (n=87) Ill group (n=20) Total in the general group (n=137)
n % n % n % n %
Comorbidity Index <5 (Moderate Comorbidity) - Pii,iii 17 19.5 Pi 4 20 Pi 21 15.3
25-44 years - - 1 1.1 - - 1 0.7
45-59 years - - Pii,iii 13 14.9 pi 4 20 pi 17 12.4
60-74 years - - 3 3.5 - - 3 2.2
75-90 years - - - - - - - -
Comorbidity index> 5 (Severe degree of comorbidity) 30 100 Pii,iii 70 80.5 Pi 16 80 Pi 116 84.7
25-44 years - - 1 1.1 - - 1 0.7
45-59 years 5 16.7 17 19.5 5 25 27 19.7
60-74 years 19 63.3 45 51.7 8 40 72 52.6
75-90 years 6 20.0 7 8.1 3 15 16 11.7
Note. pi, pll, pill - p< 0,05 compared to the corresponding group I, II, III according to Fisher test.
Assessment of IC in clinical groups, taking into account the nature of the disease (Table 6) (p<0,05), showed a relationship between the number of vascular pools affected by atherosclerosis, the severity of the clinical course of CCI and the severity of comorbidity. Thus, at atherosclerotic lesions of the vessels of all three basins (brain, heart and lower extremities), the highest values of the mean IC
value (10 points) were established. That is, patients in the first clinical group with atherosclerotic lesions of the vessels of the brain, heart and lower extremities had the highest number of the ones with a greater number of comorbid conditions than in the second and third clinical groups with the damage of two basins - vessels of the brain and heart and vessels of brain and lower extremities, respectively.
Table 6
The average value of the comorbidity index in clinical groups, taking into account the nature of CCI course
Clinical groups The average value of the index of comorbidity in points, Me (25-75%)
CCI without Acute CCI with TIA (n=15) CCI with ischemic CCI with recurrent Total (n=137)
Brain Disorders (n=23) stroke (n=59) stroke (n=40)
Clinical group I (n = 30) 10.0 (8.0-10.5) 9.5 (6.0-13.0) 8.0 (6.0-10.0) 8.0 (7.0-10.0) 8.0 (7.0-10.0)
Clinical group II (n = 87) 7.0 (6.0-8.0)* 7.0 (5.0-8.0) 6.5 (5.5-9.0) 7.0 (6.0-9.0) 7.0 (6.0-9.0)
Clinical group III (n = 20) 6.5 (6.0-7.0)* 5.5 (4.0-7.0) 6.5 (5.5-7.5) 7.5 (7.0-9.0) 7.0 (6.0-7.5)
Note. * - p <0.05 compared with group I. 80
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To assess the effect of modifiable and non-modi- analysis of the Charlson comorbidity index in R.A. fiable risk factors on the severity of comorbidity, an Deyo excluding age estimates (Table 7).
Table 7
Characteristics of the comorbidity index without taking into account age in clinical groups, taking into account age categories
Number of examined patients
The degree of severity of comorbidity I group (n=30) II group (n=87) III group (n=20) Total in the general group (n=137)
n % n % n % n %
Comorbidity Index <5 (Moderate Comorbidity) 12 40.0 Pii,iii 57 65.5 Pi 15 75.0 Pi 84 61.3
25-44 years - - 1 1.1 - - 1 0.7
45-59 years - Pii,iii 21 24.1 Pi 8 40.0 Pi 29 21.1
60-74 years 12 40.0 30 34.5 6 30.0 48 35.0
75-90 years - - 5 5.7 1 5.0 6 4.4
Comorbidity index> 5 18 60.0 30 34.5 5 25.0 53 38.7
(Severe degree of comorbidity) Pii,iii Pi Pi
25-44 years - - 1 1.1 - - 1 0.7
45-59 years 5 16.7 9 10.3 1 5.0 15 11.0
60-74 years 7 23.3 18 20.7 2 10.0 27 19.7
75-90 years 6 20.0 Pn 2 2.3 Pi 2 10.0 10 7.3
Note. pi, pll, pill - p< 0,05 compared to the corresponding group I, II, III according to Fisher point test.
Analysis of the characteristics of comorbidity severity without taking into account age showed a decrease in its severity in the selected clinical groups (Table 7). So, if age was taken into account when assessing IC, then in the I clinical group only a severe degree of comorbidity was established, and if
age was not taken into account, then in this group a moderate degree of comorbidity was established, and severe - in only 60% of cases. These data confirm the concept of the effect of age on comorbidity severity and on the number of vascular basins affected by atherosclerosis in patients with CCI.
Table 8
The average value of the comorbidity index without taking into account age in the clinical groups, taking into account the nature CCI
The average value of the index of comorbidity in points, Me (25-75%)
Clinical groups CCI without Acute CCI with TIA (n=15) CCI with ischemic CCI with recurrent Total (n=137)
Brain Disorders (n=23) stroke (n=59) stroke (n=40)
Clinical group I 7.0 7.5 5.0 7.0 7.0
(n=30) (5.5-7.5) (6.0-9.0) (4.0-7.0) (4.0-8.0) (5.0-8.0)
Clinical group II 4.0 4.0 5.0 5.0 4.0
(n=87) (3.0-6.0)* (3.0-5.0) (3.0-6.0) (3.0-7.0) (3.0-6.0)
Clinical group III 4.0 4.0 4.5 6.0 4.5
(n=20) (4.0-4.0) * (3.0-5.0) (3.0-5.0) (5.0-6.5) (3.5-5.5)
Note. * - p <0.05 separately from group I.
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The same pattern was observed when assessing the average IC value without taking into account age. There was a decrease in the severity profile of comorbidity in the subjects when comparing these indicators with a group of people where the age of the patients was taken into account (Table 6, 8). So in clinical group I with CCI without acute ischemic episodes in history, a decrease in these indicators was noted by 30%, with CCI with TIA in history -by 21%, with CCI with one stroke in history - by 37.5% and by 12.5% - with CCI with a history of repeated strokes. The same trend persisted in the second and third clinical groups with a different nature of CCI course.
Median difference of 3 points when assessing the average value of the comorbidity index taking into account age showed that age, as an unmodifiable risk factor, in 1/3 of the cases determines the comor-bidity index, which depends on the number of vascular basins affected by atherosclerosis. In 2/3 of the cases, this is a modifiable comorbid pathology (hypertension, diabetes mellitus, coronary heart disease and lower extremities, heart failure, and others), which can be controlled, compensated, and affect the nature of chronic cerebral ischemia course.
Thus, the assessment of the comorbid profile of patients with chronic cerebral ischemia on the
background of multifocal atherosclerosis showed a significant effect of modifiable and unmodifiable factors not only on the development, but also on the nature and severity of the disease course. Determining the degree of comorbidity, the sequence of occurrence or progression of comorbid diseases, both pathogenetically related and unrelated, which may depend directly or indirectly on certain age groups in patients with CCI, will allow more effective primary and / or secondary preventive measures for this disease.
CONCLUSIONS
1. It was noted that the severity of comorbidity, as assessed by the Charlson's index in the modification of R.A. Deyo, depends on age and determines the nature of the atherosclerotic lesion, as well as the severity of the clinical course of CCI.
2. It was found that the profile of comorbidity in patients with chronic cerebral ischemia on the background of multifocal atherosclerosis in 1/3 of the cases was not a modifiable factor (age), but in 2/3 of the cases - modifiable factors.
3. Assessment of the profile and severity of co-morbidity makes it possible to influence the nature of the development and course of cerebral ischemia, which is caused by systemic atherosclerotic lesions of the vascular system.
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СПИСОК Л1ТЕРАТУРИ
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10. Stroke rehabilitation evidence and comorbidity: a systematic scoping review of randomized controlled trials / L. A. Michelle Nelson, et all. Topics in Stroke Rehabilitation. 2017. Vol. 24, No. 5. No. 374-80 DOI: https://doi.org/10.1080/10749357.2017.1282412
11. Validity of the age-adjusted charlson comorbidity index on clinical outcomes for patients with nasopha-ryngeal cancer post radiation treatment: a 5-year nationwide cohort study / C. C. Yang et al. PLoS One. 2015. T. 10. № 1. C. e0117323.
URL: https://journals.plos.org/plosone/article?id=10.1371 /journal.pone.0117323.
DOI: https://doi.org/10.1371/journal.pone.0117323
Стаття надшшла до редакцп 17.09.2019
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