QUALITY OF LIFE DYNAMICS IN PATIENTS WITH DIABETIC FOOT SYNDROME WITH COMBINED TREATMENT BY PHYSIOTHERAPY AND AUTOLOGOUS PLASMA

(by 5.25 %) and «anxiety/depression» categories (by 19.74 %). PRGFT was included in the combined treatment scheme post PDT-course to stimulate epithelialization of wound defects in patients of the 2 nd group. Efficacy of this combined algorithm was confirmed by overall EuroQol scale category improvements: «mobility» — by 18 %, «self-care» — by 9 %, «usual activities» — by 9 %, «pain/discomfort» 15 % and «anxiety/depression» categories by 20 %. Conclusions. Combined photodynamic and autologous plasma rich growth factor therapy is preferable to standard therapy in the therapeutic management and improvement of quality of life in outpatients with diabetic foot syndrome.Key

According to the International Diabetes Federation in Ukraine, the number of patients with diabetes mellitus (DM) between the ages of 20 and 79 years is about 7 % of the total population [1], with an increasing estimate of approximately 629 million patients worldwide by 2045 [2]. DM is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation [3]. DM related ulcers rank first among lower extremity ulcers, which in most cases result to sensitivity loss [4]. Diabetic neuro-and angiopathy are major factors causing diabetic foot ulcers (DFU) [5], resulting from ischemic reduction of oxygen and nutrients supply to the ulcerous site, thus hindering the optimal wound healing process in such patient cohorts. In oxygen and nutrient deprived states, epithelial cells in the ulcerous site fail to release vital healing factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) [6]. Some growth factors such as epidermal growth factor (EGF), granulocyte-colony stimulating factor (GCSF), nerve growth factor (NGF) and VEGF have been evaluated in patients with DFU [7,8]. In recent studies a pool of growth factors from auto logous plasma rich growth factors were analyzed [9,10].
Health Related Quality of life (HRQoL) research has become an integral part of modern medicine. The World Health Organization (WHO) recommends the use of the following basic HRQoL criteria: physical, psychological, level of autonomy, social life and environment [11], thus the EuroQol-5D-5L (Ukrainian Version for Ukraine) questionnaire developed by the European Quality of Life Study (EuroQol Group), which was officially approved, was used to assess patients' quality of life in this study. This questionnaire demonstrates both physical and psycho-emotional indicators as well as permits quality of life assessments at different stages of the treatment process.
The aim of this study is to evaluate the efficacy of combined photodynamic therapy (PDT) and plasma rich growth factors (PRGFT) therapy on the quality of life improvement in patients with diabetic foot syndrome.

MATERIALS AND METHODS
The study included 61 outpatients with type 2 DM with Wagner grade II diabetic foot syndrome, who gave informed consent to participate in the study in accordance with the world medical association (WMA) Helsinki Declaration -Ethical Principles for Medical Research Involving Human Subjects, 2013.
Glucose-lowering therapy was supplemented with antibiotics (according to the results of microbiological examination of the discharge), while wound debridement (1 st group), in the 2 nd group (n = 31) standard therapy (ST) was supplemented by PDT and PRGFT procedures.
Initially patients were prescribed PDT using a laser machine «Lika-Surgeon M» (Photonica-Plus, Ukraine) with a wavelength of 660 nm in a continuous regiment every other day (8 procedures). Methylene blue 1 % aqueous solution as a photosensitizer was used.
After 2 weeks post wound surface cleaning and transitioning to the granulation phase, PRGFT was added to treatment process. The procedures were performed once a week, a total of 4 treatment course procedures.
In order to assess quality of life dynamics, all patients were interviewed using the EuroQol-5D-5L survey instrument, which consists of a EQ-5D descriptive system followed by the EQ visual analogue scale (EQ VAS) [13,14]. In the descriptive section, health status is measured in five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from 1 to 5 were divided into two subgroups, where scores 1, 2, and 3 corresponded to the overall quality of life scores above average; and 4 and 5 were below average.

Клінічна ендокринологія
To evaluate trophic ulcer healing dynamics, a Lesion Meter app was used. Measurements were made at each patient visit. Data for each patient were automatically stored in separate folders.
Statistical analysis was performed with Windows 10 -Office Professional Plus software (Agreement ID: V0731528) with the use of parametric and non-parametric methods of variation statistics. Shapiro-Wilk test was applied to test normality of parameters in the study. Two-sample Student's t-test was used to determine the significantly changed between groups with a probability mean of 0.05. Relative change method was used to compare ulcer healing dynamics in the two groups.

RESULTS AND THEIR DISCUSSION
Clinical status evaluation in the 1 st group demonstrated the average total score at baseline to be 13.97 points according to S(AD) SAD classification, after 2 weeks -13.20 (improvement by 5.51 %), after 6 weeks -7.83 (improvement by 43.95 %) (p > 0,05) (Tab. 1).
Clinical status improvement in patients in the 1 st group after PDT was achieved by a 19.89% inflammation reduction. Other S(AD) SAD categories had significant positive dynamics. The results obtained following PRGFT stimulation of the epithelium in the second stage showed a 30.95% decrease of the ulcer defect area, depth -by 5.00 %, improvement of angiopathy indices -by 28.93 % and neuropathy signs -15.54 % (p > 0,05).
The same positive clinic dynamics in the 2 nd group post PDT were achieved with more obvious improvement of up to 42.52 %, while positive dynamics were observed in other categories. PRGFT performed at the second stage as part of the combined treatment resulted in: 53.05 % decrease of defective ulcer area, depth -by 11.00 %, improvement indices in angiopathy category -by 43.29 %, in the neuropathic category -by 22.10 % (p < 0,05).
In the 2 nd group, quality of life dynamics after PDT demonstrated a 17.5 % improved ave rage score in «mobility», 9.15 % in «usual activities» and by 15.15 % in the «pain/discomfort» categories. Following PRGFT, improvement was achieved by 43.5 % in the «physical activity» category, 22.54 % in the «household activity» and by 33.67 % in the «pain/discomfort» categories (p < 0,05) (Tab. 4).
Unlike patients in the 1 nd group, earlier posi tive quality of life dynamics in the 2 nd group was obtained after PDT in the «anxiety/depression» and «self-care» categories by 19.74 % and 7.85 % respectively, with further improvement after PRGFT by 68.46 %, and in the «self-care» after 6 weeks -by 28.09 % (p > 0.05).
Further quality of life evaluation with Vi sual Analog Scale VAS in the 1 st group revealed a baseline total score of 41.73 points, after 2 weeks' -58.33 score points and after 6 weeks -62.37 score points, with appropriate improvement by 28.46 % and 33.09 % after standard treatment (p < 0,05). In the 2 nd group, 29.97 % post PDT and 42.69 % post PRGFT improvements were obtained (p < 0,05).
Discussion. Non-healing trophic ulcers in patients with diabetes mellitus significantly impairs quality of life and inhibits both physical and psychological status. Using PDT as combined therapy for chronic ulcers in DM patients resulted in complete purification of the wound surfaces in shorter time periods compared to ST Клінічна ендокринологія provement), «self-care» (7.85 %), «usual activities» (7.06 %), «pain/discomfort» (5.25 %) and «anxiety/depression» category (9.74%) improvements (p < 0,05). Based on contemporary data [9,10], PRGFT was included in the combined treatment scheme post PDT-course to stimulate epithelialization of the wound defects in patients of the 2 nd group. The effectiveness of the proposed algorithm was confirmed by the improvement of all categories of the EuroQol scale: «mobility» -by 18 %, «self-care» -by 9 %, «usual activities» -by 9 %, «pain/discomfort» 15 % and «anxiety/depression» categories by 20 % (p < 0.05).
Advantages of using PDT and PRGFT in sequential stages of wound healing reveals new therapeutic perspectives in regenerative medicine. This treatment scheme has obvious advantages compared to the traditional debridement. Both components have demonstrated properties for active stimulation of cell proliferation, differentiation and angiogenic potential. This approach permits healing time reduction, thus improving quality of life of DM patients.
As limitations, only local wound status dynamic effects on quality of life were evaluated, while other general conditions were not considered in the current study, aspects envisaged in future studies.

CONCLUSIONS
Photodynamic and autologous plasma rich growth factors combined therapy is preferable vis-a-vis standard care in the treatment and improvement of quality of life in outpatients with diabetic foot syndrome.