[Personalized patient-oriented approach to the treatment of musculoskeletal pain syndrome using over-the-counter medications. Resolution of the Expert Council (May 28, 2023)]. / Personalizirovannyi patsientoorientirovannyi podkhod k lecheniyu skeletno-myshechnogo bolevogo sindroma s ispol'zovaniem bezretsepturnykh preparatov. Rezolyutsiya ekspertnogo soveta (28 maya 2023 g.).

Diseases of the musculoskeletal system in Russia affect 19.2 million people. Untimely diagnosis and inadequate therapy of pain syndrome negatively affect the daily functioning and quality of life of patients, and create significant socioeconomic problems. The most common variants of musculoskeletal pain (MSP) are osteoarthritis (OA) and low back pain (LBP). OA is seen in 57.6% of individuals over 65 years of age. It should be noted that chronic pain syndrome, rather than anatomical and degenerative changes detected by imaging studies, determines to a greater extent the quality of life of patients with OA and prognosis during the course of the disease. The global burden of disability associated with LBPD increased in all age groups between 1990 and 2019 and was highest in the 50-54 age group.

[Real-world experience with netakimab in the treatment of spondyloarthritis].

AIM: To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). MATERIALS AND METHODS: The retrospective analysis included 23 patients (13 males; 56.5%) aged 23 to 73 years (median 42, interquartile range 28 to 52 years) with AS (n=12) or PsA (n=11) who received netakimab therapy from February 2021 to April 2023. Disease activity was assessed every 3-6 months based on the C-reactive protein (CRP) level for all patients according to the BASDAI and ASDAS-CRP indices for AS, DAPSA and PASI for PsA. These indicators were analyzed before therapy and at the last visit to assess the effectiveness of treatment. The results are presented as median (interquartile range). RESULTS: In all patients treated with netakimab (median duration of treatment 11 months), the CRP level decreased from 10.6 (3.1; 17.3) to 3.1 (1.9; 8.9) mg/L (absolute difference -7.5 mg/L, median relative reduction -60%; p=0.008), and the proportion of patients with elevated CRP decreased from 70 to 41%; p=0.039. In patients with AS (median duration of treatment 9 months), BASDAI score decreased from 5.8 (4.7; 6.5) to 3.0 (1.9; 3.8) points (absolute difference -2.8 points, median relative reduction of -45%; p=0.008) and ASDAS-CRP score decreased from 2.8 (1.9; 3.9) to 1.9 (1.7; 2.6) points (absolute difference -0.9 points, median relative reduction -21%; p=0.007). The proportion of patients with high AS activity (BASDAI≥4) decreased from 90% to 20% (p=0.031); however, there was no significant change in the CRP level (absolute difference -4.9 mg/L, median relative reduction -57%; p=0.110). In patients with PsA (median duration of treatment 18 months), the CRP level decreased from 12.0 (4.5; 17.3) to 3.3 (2.0; 7.8) mg/L (absolute difference -8.7 mg/L, median relative reduction -80%; p=0.041), the DAPSA score decreased from 23.0 (19.0; 30.5) to 6.3 (5.2; 13.5) points (absolute difference -16.7 points, median relative reduction -69%; p=0.018). Three (13%) patients reported mild to moderate adverse events. CONCLUSION: The obtained data confirm the effectiveness and safety of netakimab in treating AS and PsA in real-world practice.

On the accuracy of Covid-19 forecasting methods in Russia for two years.

The effectiveness of predicting the dynamics of the coronavirus pandemic for Russia as a whole and for Moscow is studied for a two-year period beginning March 2020. The comparison includes well-proven population models and statistic methods along with a new data-driven model based on the LSTM neural network. The latter model is trained on a set of Russian regions simultaneously, and predicts the total number of cases on the 14-day forecast horizon. Prediction accuracy is estimated by the mean absolute percent error (MAPE). The results show that all the considered models, both simple and more complex, have similar efficiency. The lowest error achieved is 18% MAPE for Moscow and 8% MAPE for Russia.

[The prevalence of anemia and its associations with other geriatric syndromes in subjects over 65 years old: data of Russian epidemiological study EVKALIPT].

BACKGROUND: A low hemoglobin level in older adults impairs cognitive ability and functional status and associates with risk of falls and fractures, sarcopenia, malnutrition, depression, frailty, and decreased autonomy. Epidemiological data on the anemia prevalence in the geriatric population in our country is not available. AIM: To assess the prevalence of anemia and analyze its associations with geriatric syndromes (GS) in subjects aged 65 years. MATERIALS AND METHODS: 4308 subjects (30% of men) aged 65107 years, living in 11 regions of the Russian Federation, were examined and divided into age groups (6574 years, 7584 years and 85 years). All the participants underwent a comprehensive geriatric assessment and determined hemoglobin level. RESULTS: The anemia prevalence in older adults was 23.9%. It has been shown that with an increase in age per 1 year, the risk of anemia detection increases by 4%. The incidence of anemia was higher in males than females (28.1% versus 22.1%; p0.001). In most cases, anemia was mild. The results of a comprehensive geriatric assessment show that patients with anemia had lower hand grip force, Barthel Index, the sum of points on Lawton instrumental activities of daily living scale, Mini Nutritional Assessment scale, the Mini-Cog test and higher the sum of points on the Geriatric Depression Scale (GDS-15) and the Age Is No Barrier scale. Patients with anemia were more likely to use hearing aids, absorbent underwear, and assistive devices during movement. Patients with anemia had a higher incidence of all GS, except for orthostatic hypotension and chronic pain syndrome. The presence of GS is associated with an increased risk of anemia by 1.33.4 times. CONCLUSION: EVKALIPT study obtained domestic data on the prevalence of anemia in older patients and examined its associations with other GS.

[Effect of bone anabolic therapy on bone remodeling and bone density in geriatric patients with osteoporosis and falling syndrome].

BACKGROUND: Older adults with severe osteoporosis are the most vulnerable group of geriatric patients. They are shown the purpose of anti-osteoporotic therapy, which should be effective and safe. Teriparatide showed a decrease in the risk of fractures, an increase in BMD. In Russia, the use of teriparatide in the geriatric population is extremely scarce. AIM: assess clinical course, bone metabolism parameters and efficacy of bone-anabolic therapy in elderly and senile patients with severe osteoporosis and falls. MATERIALS AND METHODS: The longitudinal prospective study included 100 patients 60 years and older with severe osteoporosis who had one or more falls within the last year. All patients were prescribed calcium and vitamin D preparations and bone-anabolic therapy (teriparatide 20 mg daily subcutaneously). The duration of follow-up was 24 months and included 3 visits: screening, at 12 and 24 months. The effectiveness of bone-anabolic therapy was carried out on the basis of assessing the frequency of new fractures, reduction of pain, changes in BMD according to X-ray densitometry, dynamics of bone metabolism markers. RESULTS: All patients had severe osteoporosis and aggravated comorbidity status, suffered a fall within the last year, and also low-energy fractures in the past. One in three patients had a vertebral fracture, one in five had a proximal femoral fracture. Prior to the start of the study, 61 patients received antiosteoporotic therapy. During the follow-up, 4 patients died, 96 patients completed the study. Against the background of teriparatide therapy, a decrease in the number of new cases of low-energy fractures and the number of patients with chronic pain was obtained. An increase in BMD was noted in the lumbar spine after 24 months and in the femoral neck after 12 months. There was no negative dynamics of the BMD. Also after 12 months, an increase in P1NP and C-terminal telopeptide of collagen type 1 was noted, after 24 months - osteocalcin and C-terminal telopeptide. CONCLUSION: The use of teriparatide can be recommended as an effective intervention to treat severe osteoporosis in geriatric patients with falls.

[Comprehensive personalized protocol for the prevention of repeated falls in elderly and senile patients]. / Kompleksnyi personifitsirovannyi protokol profilaktiki povtornykh padenii u patsientov pozhilogo i starcheskogo vozrasta.

OBJECTIVE: To study evaluation of the effectiveness of a comprehensive personalized protocol for the prevention of repeated falls in elderly and senile patients. MATERIAL AND METHODS: Over the course of one year, 300 patients aged 60 and older who suffered two or more falls during the year were observed. Patients of group 1 (n=100) were recommended a comprehensive personalized protocol for the prevention of repeated falls, the observance of which was regularly monitored; patients of group 2 (n=100) received standard recommendations for the prevention of falls upon discharge from the hospital, the observance of which was not actively monitored; patients of group 3 (n=100) were observed by a therapist on an outpatient basis. Primary endpoints: frequency of falls, death from any cause; secondary endpoints: the frequency of fractures, the frequency of hospitalizations for any reason. RESULTS: In group 1, after a year, the frequency of falls decreased by 5 times (100% vs. 21%, p<0.0001), in groups 2 and 3 - by 38% (p=0.013) and 81% (p<0.001). There was no significant decrease in the number of all fractures in any group, but in group 3, the frequency of vertebral fractures increased during the year (p=0.029). Statistically significant positive dynamics of indicators characterizing the geriatric status has been established: walking speed, values on the basic activity scale, a short nutrition assessment scale, the results of the drawing hours test have increased, the intensity of pain has decreased. No one died in group 1, unlike 5 patients in group 2 and 8 in group 3 (p=0.011). CONCLUSION: The use of a comprehensive personalized protocol for the prevention of repeated falls can reduce the number of complications in elderly and senile patients.

Toward single-molecule surface-enhanced Raman scattering with novel type of metasurfaces synthesized by crack-stretching of metallized track-etched membranes.

The effect of hyperenhancement of Raman scattering (RS) appearing on microcracks of the metal deposition (silver and gold) of uniaxially stretched polymer track-etched membranes is investigated. Deformation of membranes with a combination of high surface density and small diameter of their pores leads to the development of many microcracks in the metal coating. The efficiency of the surface enhancement RS (SERS) of the synthesized metasurfaces has been investigated on the example of organic compound malachite green, and the possibility to recognize extremely low fractions of the substance was demonstrated. An increase in the SERS signal with an increase in the deformation of the samples and even greater enhancement after their unloading and relaxation were found. The experiment on tensile strain and relaxation of the deformation of the samples and the consequent change in their electrical conductivity confirm the assumption that SERS appears on microcracks edges with a rather small distance between their boundaries. The SERS technique is proposed to analyze the formation of micro- and nanocracks on metal coatings.

Baseline Accuracies of Forecasting COVID-19 Cases in Russian Regions on a Year in Retrospect Using Basic Statistical and Machine Learning Methods.

The large amount of data accumulated so far on the dynamics of the COVID-19 outbreak has allowed assessing the accuracy of forecasting methods in retrospect. This work compares several basic time series analysis methods, including machine learning methods, for forecasting the number of confirmed cases for some days ahead. Year-long data for all regions of Russia has been used from the Yandex DataLens platform. As a result, accuracy estimates for these basic methods have been obtained for Russian regions and Russia as a whole, in dependence on the forecasting horizon. The best basic models for forecasting for 14 days are exponential smoothing and ARIMA, with an error of 11-19% by the MAPE metric for the latest part of the course of the epidemic. The accuracies obtained can be considered as baselines for more complex prospective models.

[Characteristics of geriatric and somatic status in patients with osteoporosis].

BACKGROUND: Older adults with osteoporosis (OP) and high risk of falls are the most vulnerable group of patients with respect to the development of fractures. Falls and fractures in elderly patients with OP are associated with geriatric syndromes and worse functional status. AIM: To аssess comorbidity and geriatric status in elderly and senile patients with and without OP. MATERIALS AND METHODS: The study included 607 patients over 60 years of age hospitalized in the geriatric department. According to the presence of OP, the patients were divided into 2 groups: group 1 - patients with OP (n=178, 29.3%), group 2 - patients without OP (n=429, 70.7%). All patients underwent a general clinical study, an assessment of comorbidity -according to the Charlson index, and a comprehensive geriatric score. RESULTS: OPs had 178 (29.3%) patients, more often these were women. 55.6% of patients with OP were disabled. Age--related diseases such as Alzheimer's disease, Parkinson's disease, osteoarthritis, anemia, thyroid disease, varicose veins were significantly more common in patients with OP. With almost all of these diseases, a univariate analysis revealed an association with OP. Geriatric syndromes such as frailty, hypodynamia, malnutrition, polypharmacy, urinary incontinence were significantly more common in group 1 patients. Patients with OP were more likely to live alone and use mobility aids compared to patients without OP.The univariate analysis demonstrated that OP is associated (OR 1.54 to 2.00) with frailty, hypodynamia, the use of aids in movement, sleep disorders, sensory vision deficiency, urinary incontinence. The Functional status of patients with OP was worse compared to patients without OP. Patients with OP suffered more fractures, and vertebral fractures were significantly more frequent. CONCLUSION: Patients with OP have a high comorbidity, a burdened geriatric status. In elderly patients, it is necessary not only to screen and diagnose OP, to assess the risk of 10-years probability of major pathological fractures using the FRAX algorithm, but also to conduct a comprehensive geriatric assessment to diagnose geriatric syndromes that weaken the course of OP and lead to more serious consequences.

[The prevalence of osteoarthritis and its association with geriatric syndromes in people over 65: data from the Russian epidemiological study EVKALIPT].

BACKGROUND: Osteoarthritis (OA) in elderly and senile patients is not only common, but also one of the main diseases affecting the duration of active life, its quality, the appearance of addictions and loss of autonomy. Data on the relationship between OA and geriatric syndromes (GS) in our country are extremely scarce. AIM: To estimate the prevalence of OA and to analyze its associations with HS in persons aged 65 years. MATERIALS AND METHODS: The study included 4308 people (30% of men) aged 65 to 107 years, living in 11 regions of Russia. The patients were divided into 2 groups: with OA (n=2464) and without OA (n=1821). All patients underwent a comprehensive geriatric assessment. RESULTS: The prevalence of OA was 57.6%. With age, the frequency of OA increased significantly. According to the results of a comprehensive geriatric assessment, patients with OA had lower walking speed, the sum of points on the Bartel, Lawton scales and a short battery of physical functioning tests and higher the sum of points on the geriatric scale of depression and the age is not a hindrance scale. Patients with OA rated the quality of life and health status lower and higher the intensity of pain syndrome. Patients with OA were more likely to use any assistive device, with the exception of a wheelchair. In patients with OA, the most common HS were chronic pain syndrome (92%), senile asthenia syndrome (64%), basic (66%) and instrumental (56%) dependence in everyday life, cognitive impairment (62%), probable depression (51%) and urinary incontinence (50%). Univariate regression analysis showed that OA is associated with a 1.23.0-fold increase in the risk of a number of GS and a 28% decrease in the risk of malnutrition. CONCLUSION: OA is widespread in the elderly population. The presence of OA is associated with a number of GS associated with loss of autonomy.

[Anemia in the elderly: influence on physical, functional status and prognosis.]

Anemia in older patients can be seen as a geriatric syndrome that impairs quality of life, functional status, reduces autonomy, and affects prognosis. Anemia is associated with other geriatric syndrome such as frailty, sarcopenia, falls and fractures, vitamin D deficiency, dementia and others. Iron deficiency anemia is the most common. Most often in older persons, the causes of its development are chronic blood loss and malnutrition. Laboratory criteria confirming iron deficiency anemia are hemoglobin reduction, microcytosis, low serum iron and ferritin. This is the basis for the administration of iron preparations, among which two- and threevalent ones are isolated. Trivalent iron preparations are most preferred in older patients because they have better tolerance and less frequency of side effects with comparable efficacy with divalent preparations.

[The efficacy and safety of intra-articular application of a combination of sodium hyaluronate and chondroitin sulfate for osteoarthritis of the knee: a multicenter prospective study].

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study. MATERIALS AND METHODS: 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements. RESULTS: Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake. CONCLUSION: These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.

[Falls and pathology of the musculoskeletal system in the older age groups]. / Padeniia i patologiia kostno-myshechnoi sistemy v starshikh vozrastnykh gruppakh.

BACKGROUND: Fall in the elderly is considered as a geriatric syndrome, which increases the risk of new falls, decreases physical functioning and autonomy and is associated with other geriatric syndromes. One of the most common risk factors for falls is the pathology of the musculoskeletal system, including osteoarthritis, sarcopenia, osteopenia and osteoporosis, as well as chronic pain. AIM: To characterize diseases of the musculoskeletal system in elderly patients with falls. MATERIAL AND METHODS: The study included 289 patients (mean age 75,8±7,9 years, 224 women) who underwent falls during the last year. All patients had polymorbid pathology (mean number of diseases 5,13±2,3, the Charlson index 5,63±1,8 points). All patients underwent general clinical studies, a comprehensive geriatric assessment, X-ray examination of the joints, dual-energy X-ray absorptiometry. RESULTS AND CONCLUSION: The risk of falls assessed with a self-assessment scale as 7,45±3 points had 90,3% of patients, 34,6% of patients had the high hospital risk of falls. All patients had aggravated geriatric status (on average 7 geriatric syndromes). Among the risk factors for falls, one of the most common was the condition associated with the pathology of the musculoskeletal system: chronic pain (84,7%), physical inactivity (56,1%), disorders of balance (60,2%) and gait (35,9%), the use of mobility aids (30,4%), orthopedic pathology (9,7%) and vitamin D deficiency (86,1%). Osteoarthritis prevailed (75,8%) among nosological forms. One hundred and forty-two (64,8%) patients had pain in the joints, the duration of pain was 6,2±5,6 days, the pain intensity was 47,2±20,7 mm on a visual analogue scale and 106,3±112,3 points by WOMAC. The neuropathic component was diagnosed on DN4 scale in 34 (23,9%) patients. Dynapenia was detected in 109 (37,7%) patients, and sarcopenia in 28 (25,6%) of them. The risk of osteoporotic fractures was 17,4±7,9%. The significantly higher incidence of dynapenia, insufficiency and deficiency of vitamin D and a higher risk of osteoporotic fractures was observed in 289 patients with falls compared to 213 people without falls.

[Osteoarthritis and geriatric syndromes]. / Osteoartrit i geriatricheskie sindromy.

AIM: To study the geriatric status of patients with osteoarthritis (OA) older than 60 years depending on the severity of frailty. MATERIAL AND METHODS: The study included 201 patients with OA (mean age 75.84±8.09 years). The patients were divided into 3 groups: patients without frailty, patients with prefrailty and patients with frailty. Along with clinical examination, the risk of falls, pain intensity, the Charlson comorbidity index and the number of geriatric syndromes were calculated. RESULTS AND CONCLUSION: With the increase of frailty, the number of patients experiencing difficulties in movement increases. The physical activity of the patients gradually reduces with the appearance of prefrailty and significantly reduces in OA. At the same time, there is the increase in dependence on outside help, the decrease in IADL and walking speed. The most common geriatric syndromes in patients with OA are sensory deficits, chronic pain syndrome and falls. The neuropathic component of pain is diagnosed in every tenth patient with OA without frailty and in every third patient with OA and frailty. In light of results obtained in the study, the authors suggest detailed recommendations for treatment of patients.

[The place of chondroitin sulfate and glucosamine sulfate in osteoarthritis pain therapy: a practical view from evidence-based medicine]. / Mesto khondroitina sul'fata i gliukozamina sul'fata v terapii boli pri osteoartrite.

Osteoarthritis is one of the leading causes of a chronic pain in elderly people. Old and very old age in itself is a risk factor of a comorbidity, which often limits the therapy specified in clinical recommendations. First of all, it concerns NSAID. In such situations, priority is given to chondroitin sulfate (CS) and glucosamine sulfate (GS) having the anti-inflammatory properties comparable with effects of NSAID. CS and GS also promote the delay in progression of degenerative processes and restoration of the structure of cartilaginous tissue. The drugs of CS and GS groups are Chondroguard and Sustaguard Artro having the considerable evidence-based efficacy and safety and also a polymodality of effects in patients with a combination of osteoarthritis and socially important diseases (atherosclerosis, diabetes mellitus type 2, oncological diseases) and also geriatric syndromes (sarcopenia) and aging in general.

[Chronic pain in patients older than 60 years: a view of the geriatrics]. / Khronicheskaia bol' u patsientov starshe 60 let: vzgliad geriatra.

AIM: To analyze the geriatric status of patients with chronic pain. MATERIAL AND METHODS: One hundred and sixteen patients of a geriatric unit, aged 75.66±7.98 years (110 women, 94.8%), were studied. All patients underwent general clinical examination and complex geriatric assessment, on the results of which geriatric syndromes were identified. Characteristics of pain syndrome (cause, intensity, localization) are described. RESULTS: Chronic pain syndrome is identified in 85 (73.3%) patients. Most often pain is localized in large joints (n=44 (51.76%)) and back (n=50 (58.8%)). The intensity of pain was higher in patients with moderate dependence in daily activities compared to those with mild dependence (p<0.05). Pain intensity is associated with the degree of impairment of physical functioning (p<0.05). Patients with chronic pain have more geriatric symptoms (6.8±2.8). More syndromes (9.11±2.37) are identified in patients with marked impairment of physical functioning. The reduction of muscle strength is observed in 45.9% patients with- and 9.7% patients without chronic pain syndrome. The velocity of pace is 0.59 m/s and 0.71 m/s, respectively. CONCLUSION: The high prevalence of chronic pain in patients of a geriatric unit is shown. The intensity of pain iss higher in patients with moderate dependence in daily activities compared to those with mild dependence. Pain intensity increases with the reduction of patient's physical functioning. Patients with chronic pain more often have dynapenia and significantly lower velocity of pace that indicates the poor outcome in elderly patients.

Safety of nonsteroidal anti-inflammatory drugs in patients with cardiovascular risk.

The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes. Keywords: nonsteroidal anti-inflammatory drugs, cardiovascular diseases, cardiovascular risk, lornoxicam, diclofenac sodium, thrombo-elastogram, myocardial infarction, stroke.

Graphene Oxide as a Multifunctional Platform for Intracellular Delivery, Imaging, and Cancer Sensing.

Graphene oxide (GO), the most common derivative of graphene, is an exceptional nanomaterial that possesses multiple physical properties critical for biomedical applications. GO exhibits pH-dependent fluorescence emission in the visible/near-infrared, providing a possibility of molecular imaging and pH-sensing. It is also water soluble and has a substantial platform for functionalization, allowing for the delivery of multiple therapeutics. GO physical properties are modified to enhance cellular internalization, producing fluorescent nanoflakes with low (<15%) cytotoxicity at the imaging concentrations of 15 µg/mL. As a result, at lower flake sizes GO rapidly internalizes into HeLa cells with the following 70% fluorescence based clearance at 24 h, assessed by its characteristic emission in red/near-IR. pH-dependence of GO emission is utilized to provide the sensing of acidic extracellular environments of cancer cells. The results demonstrate diminishing green/red (550/630 nm) fluorescence intensity ratios for HeLa and MCF-7 cancer cells in comparison to HEK-293 healthy cells suggesting a potential use of GO as a non-invasive optical sensor for cancer microenvironments. The results of this work demonstrate the potential of GO as a novel multifunctional platform for therapeutic delivery, biological imaging and cancer sensing.

[The clinical status and treatment options for osteoarthritis in patients with frailty].

Aging is an independent risk factor for the development of many diseases and geriatric syndromes. Osteoarthritis (OA), as the most common joint disease in the elderly, can be attributed to age - associated conditions. And the most significant geriatric syndrome, which dramatically affects the management and prognosis of an elderly, is frailty. The review provides current information on the prevalence of OA and frailty, their clinical and prognostic significance, and also shows the mutually aggravating role of these two conditions. The difference between non - and medication management of patients with OA and frailty is emphasized.

Micro-Refractometry and Local-Field Mapping with Single Molecules.

The refractive index n is one of the most important materials parameters of solids and, in recent years, has become the subject of significant interdisciplinary interest, especially in nanostructures and meta-materials. It is, in principle, a macroscopic quantity, so its meaning on a length scale of a few nanometers, i.e., well below the wavelength of light, is not clear a priori and is related to methods of its measurement on this length scale. Here we introduce a novel experimental approach for mapping the effective local value [Formula: see text] of the refractive index in solid films and the analysis of related local-field enhancement effects. The approach is based on the imaging and spectroscopy of single chromophore molecules at cryogenic temperatures. Since the fluorescence lifetime T1 of dye molecules in a transparent matrix depends on the refractive index due to the local density of the electromagnetic field (i.e., of the photon states), one can obtain the local [Formula: see text] values in the surroundings of individual chromophores simply by measuring their T1 times. Spatial mapping of the local [Formula: see text] values is accomplished by localizing the corresponding chromophores with nanometer accuracy. We demonstrate this approach for a polycrystalline n-hexadecane film doped with terrylene. Unexpectedly large fluctuations of local-field effects and effective [Formula: see text] values (the latter between 1.1 and 1.9) were found.