[Management of patients with insomnia and polymorbidity. A draft of the clinical guidelines]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii. Proekt klinicheskikh rekomendatsii. Obshcherossiiskaya obshchestvennaya organizatsiya «Rossiiskoe obshchestvo somnologov¼.

Insomnia is a serious and widespread public health problem, but is often undetected and patients do not receive needed treatment. Insomnia is often comorbid with other diseases and conditions, such as arterial hypertension, type 2 diabetes mellitus, pain syndromes, anxiety and depressive disorders, etc. A separate problem is drug-induced insomnia, when patients develop symptoms due to other diseases treatments. Insomnia has a negative effect on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and decreased quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so clinical guidelines draft for the evaluation and treatment of insomnia in multimorbid patients is proposed. Diagnostic methods are reviewed and recommendations are given for the treatment of acute and chronic insomnia and features of the treatment of insomnia in multimorbid patients. A clinical algorithm has been proposed to determine treatment tactics in multimorbid patients.

[Drug-induced cognitive impairment and dementia]. / Lekarstvenno-indutsirovannye kognitivnye narusheniya i dementsiya.

One of the reasons for the development or worsening of cognitive impairment (CI) may be the use of a number of drugs: non-steroidal anti-inflammatory drugs, antiarrhythmics, antidepressants, glucocorticosteroids, antitumor drugs and a number of others. The negative effect of drugs on cognitive functions is realized due to many pathophysiological mechanisms: disruption of hormonal regulation, decreased neuronal excitability, increased activity of gamma-aminobutyric acid receptors, decreased cerebral circulation, atrophic changes in the brain; many mechanisms have not been fully established. Risk factors for the development of drug-induced CIs are: old age or childhood, brain damage, chronic diseases, genetic factors, the patient's initial CI, polypharmacy, dose and duration of drug use, acute infectious diseases, metabolic disorders, dehydration, acute urinary retention, etc. To diagnose and differentially diagnose drug-induced CI, it is necessary to establish a connection between the start of taking a suspected drug-inducer and a decrease in cognitive functions. The first step in the treatment of drug-induced CI is the abolition of an inducer drug or a reduction in its dose, in cases where it is impossible to discontinue the drug and there is no replacement, special slow-release dosage forms can be considered. The main measures to prevent drug-induced CI include the use of drugs with the lowest risk of their development, assessment of drug interactions, and the use of modern scales to assess the risk of developing this side-effect (anticholinergic burden scale, etc.).

[Management of patients with insomnia and polymorbidity: expert consensus]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii: konsensus ekspertov.

Sleep disorders are becoming increasingly important due to the high comorbidity with other diseases and a significant impact on the patient's quality of life. Insomnia is the most common sleep disorder both in the general population and in patients with multimorbid pathology. Its prevalence in the general population is 6-15%, while in patients with somatic diseases it increases up to 20-40% and can reach 90% in patients with comorbid mental disorders. Another problem is the development of drug-induced insomnia. Insomnia has negative impact on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and a worse quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so it is extremely important to identify and correct these disorders in the early stages, therefore recommendations for the diagnosis of insomnia in polymorbid patients are proposed. Modern methods of treating acute and chronic insomnia and features of insomnia treatment in polymorbid patients are also discussed.

[Modern issues of improving the prognosis in patients with atrial fibrillation after ischemic stroke].

The anticoagulant therapy with a priority of direct oral anticoagulants is an approach to the prevention of recurrent stroke in patients with atrial fibrillation (AF) that has presently proved its efficacy and is stated in international clinical guidelines. An extensive evidence-based database demonstrates advantages of rivaroxaban over other drugs of this class in secondary prevention of stroke in AF. Furthermore, these advantages are combined with the optimal safety profile. The rivaroxaban treatment may provide the most favorable prognosis due to the prevention of recurrent stroke in AF, reducing the rate of kidney disease progression, and slowing vascular atherosclerosis. An important beneficial feature of rivaroxaban is once-a-day intake, which is important in the context of a high incidence of cognitive disorders in this patient category, and may improve their compliance and, thus, help achieving the expected profile of treatment efficacy. Thus, rivaroxaban can be regarded as a drug of choice for secondary prevention of stroke in AF.

Thiazide and thiazide-like diuretics: how to make the right choice?

Most patients with arterial hypertension (AH) require a combination treatment to achieve the goal blood pressure. According to Russian and international clinical guidelines on the treatment of AH patients, various antihypertensive drugs may be combined; however, not all combinations have similar profiles of safety and clinical efficacy. In this respect, special attention is given to combinations of renin-angiotensin-aldosterone system inhibitors and thiazide (hydrochlorothiazide) or thiazide-like (chlortalidone, indapamide) diuretics. Diuretics also differ in their mechanisms of action, presence of pleiotropic effects and organ-protective properties, effects on the prognosis, and in the evidence base. This review discusses the place of thiazide and thiazide-like diuretics in the treatment of patients with AH and provides an evaluation of major differences in pharmacological and clinical effects of drugs of the diuretic class.

[Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)]. / Rezul'taty mezhdunarodnogo mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniya otsenki effektivnosti i bezopasnosti posledovatel'noi terapii patsientov s khronicheskoi ishemiei mozga preparatami Meksidol i Meksidol FORTE 250 (issledovanie MEMO).

OBJECTIVE: To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). MATERIAL AND METHODS: An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 - 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. RESULTS: According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. CONCLUSION: The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated.

[The problem of vitamin B12 deficiency: relevance, diagnosis and targeted therapy (based on materials of an interdisciplinary expert council with international participation)]. / Problema defitsita vitamina B12: aktual'nost', diagnostika i targetnaya terapiya (po materialam mezhdistsiplinarnogo soveta ekspertov s mezhdunarodnym uchastiem).

Deficiency of vitamin B12 occurs much more often than it is commonly believed and leads to a wide range of various disorders, the emergence of primarily neurological manifestations, while there is a lack of awareness among clinicians in the field of its causes, nonspecific manifestations, diagnostic methods and effective therapy. The conference «The problem of vitamin B12 deficiency and the experience of use in Germany¼ was devoted to this urgent clinical problem, within the framework of which an interdisciplinary council of experts, at which the most pressing issues were considered, associated with B12 deficiency.

[Herpangina. Clinical case]. / Gerpeticheskaya angina ­ aktual'naya problema otorinolaringologicheskoi praktiki.

Enterovirus infections are a group of acute infectious diseases caused by enteroviruses (including Coxsackie A and B viruses, ECHO viruses), which clinically present symptoms of damage to the central nervous system, cardiovascular system, gastrointestinal tract, muscular system, mucous membranes and skin, fever. This article presents a clinical case of patient L., 12 years old, who admitted to an otorhinolaryngologist with clinical manifestations of herpangina. The diagnosis was confirmed by PCR. The patient was prescribed, adequate rehydration, diet with the exclusion of salty, spicy and fried foods, restriction of physical activity, exclusion of thermal procedures, Benzydamine Spray (Oralsept) 0.255 mg/dose, 6 doses 3 times/day, topically, on demand and inosine pranobex (Groprinosin) in a daily dose of 50 mg/kg of body weight: 1 tablet 500 mg 4 times a day for 7 days (at the rate of 1 tablet of 500 mg per 10 kg of body weight; for a patient weighing 41 kg - 4 tablets per day). On the 10th day from the onset of the disease, the docter noted a complete regression of clinical symptoms and the patient was discharged with recovery.

[What do we Mean by "Ideal" Blood Pressure Control?]

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.

[Drug-induced uveitis]. / Lekarstvenno-indutsirovannyi uveit.

In recent years, an increasing amount of attention has been paid to medicinal products as possible risk factors in the development of eye diseases. The frequency of diagnosed drug-induced uveitis is growing yearly, which can be attributed to the appearance of new drugs - biological agents (immune checkpoint inhibitors, BRAF and MEK inhibitors, vascular endothelial growth factor inhibitors, tumor necrosis factor-α inhibitors), as well as systemic bisphosphonates and some antiviral drugs. The time interval between the beginning of the drug use and the appearance of uveitis symptoms varies from several days to months. Common symptoms include eye pain, photophobia, the appearance of floating opacities, and reduced vision associated with active inflammatory changes in the retina and optic nerve and outcomes of those inflammations. Timely diagnosis, cancellation of the drug that caused uveitis and appointment of adequate anti-inflammatory therapy in most cases effectively stops the symptoms of the disease, which determines the relevance of attention to the prevalence, pathogenesis, diagnosis and treatment of drug-induced uveitis.

[Drugs affecting obstructive sleep apnea syndrome]. / Vliyanie lekarstvennykh sredstv na sindrom obstruktivnogo apnoe sna.

Sleep-disordered breathing is one of the most common sleep-associated disorders. At the same time, their prevalence tends to increase with age. One of the most common forms of respiratory failure during sleep is obstructive sleep apnea syndrome (OSA), which is characterized by repeated episodes of cessation of breathing or a significant decrease in respiratory flow while maintaining respiratory effort as a result of obstruction of the upper respiratory tract. Drugs have different effects on OSA. There are drugs that worsen OSA, drugs that do not affect OSA, and drugs that improve OSA. Benzodiazepines, opioids, muscle relaxants, and male hormones adversely affect OSA. Also of clinical interest are drugs that do not affect OSA and can even potentially improve respiratory function during sleep. These include anti-inflammatory drugs, diuretics, bronchodilators, acetylcholinesterase inhibitors, antiparkinsonian, decongestant drugs, drugs for intranasal use, topical soft tissue lubricant, female sex hormones. Finally, the effect of a number of drugs on OSA is not definitively established and requires further study (benzodiazepine receptor agonist hypnotics, angiotensin-converting enzyme inhibitors, opiate receptor antagonists, antidepressants, proton-pump inhibitors, TNF-α antagonists, glutamate receptor antagonists, drugs for the treatment of acromegaly, drugs for the treatment of narcolepsy). Raising awareness of doctors of different specialties about the impact of various drugs on OSA can not only prevent the deterioration of respiratory distress during sleep, but also, with a rational individual approach, makes it possible to even improve the quality of sleep and blood saturation, thereby contributing to a more favorable course of OSA and the underlying disease.

[Efficacy and safety of mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)]. / Effektivnost' i bezopasnost' Meksidola u patsientov raznykh vozrastnykh grupp v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta (rezul'taty subanaliza randomizirovannogo dvoinogo slepogo mul'titsentrovogo platsebo-kontroliruemogo v parallel'nykh gruppakh issledovaniya EPIKA).

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.

[Drug-induced toxic optic neuropathy]. / Lekarstvenno-indutsirovannaya toksicheskaya opticheskaya nevropatiya.

Drug-induced optic neuropathy is a group of disorders in which medications cause degeneration of the optic nerve. The true prevalence of drug-induced neuropathy has not been studied, although the percentage of patients who develop optic nerve damage is known for individual medications. The common pathophysiological mechanisms are believed to be mitochondrial damage and imbalance of intracellular and extracellular free radical homeostasis. Typical symptoms of drug-induced neuropathy are reduced visual acuity in the central area, which is often bilateral, visual field disturbances, dyschromatopsia, and edema of the optic nerve head. Early detection of drug-induced optic neuropathy can potentially prevent or minimize serious complications. For patients who develop drug-induced optic neuropathy, treatment is based on timely diagnosis and cancellation of the provoking drug. In most patients, vision usually recovers a few weeks or months after discontinuation of previous therapy, but there have been cases of irreversible vision loss. In addition to withdrawal of the drug that caused optic nerve lesion, treatment of drug-induced neuropathy may include use of drugs and treatment methods prescribed by neurologists for peripheral neuropathy, however, such treatment is seldom based on evidence.

[Rhinitis medicamentosa]. / Lekarstvenno-indutsirovannyi rinit.

One type of non-allergic non-infectious rhinitis is represented by a heterogeneous group of rhinitis medicamentosa, which can be divided into several pathogenetic types. The most common rebound nasal congestion associated with the use of topical decongestants. Excessive use of intranasal decongestants leads to a decrease in the number of alpha-adrenoreceptors on the surface of cell membranes and uncoupling their connection with the G-protein and the development of tachyphylaxis. To prevent the development of rebound nasal congestion caused by topical decongestants, it is important to limit the frequency of their use. In most cases, the duration of the use of vasoconstrictor drugs should be limited to 5-7 days, according to Patient information leaflets for the drugs. However, in patients who have had a history of episodes of rebound nasal congestion, which develops including the previously indicated periods, the duration of decongestant therapy should be limited to 3 days. Rhinitis associated with local inflammation is caused by the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs. Currently, the so-called "aspirin triad" is well known - a combination of bronchial asthma, rhinosinusitis (often polyposis) and intolerance to ASA. Neurogenic rhinitis develops due to the use of drugs that violate vascular tone, for example, antihypertensive drugs or type 5 phosphodiesterase inhibitors. Drug-induced rhinitis has a significant impact on the patient's quality of life: nasal congestion, rhinorrhea, secondary night apnea, insomnia as a result of nasal breathing disturbances, headaches, irritability, weakness after sleepless nights disturb patients to a large extent. Timely diagnosis and withdrawal of a provocative drug, the use of topical corticosteroids in case of severe rhinitis are the basis of the treatment of rhinitis medicamentosa. In severe cases, there is a need, including surgical treatment, such as, for example, submucosal laser destruction of the lower nasal concha.

[Drug-induced restless legs syndrome]. / Lekarstvenno-indutsirovannyi sindrom bespokoinykh nog.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by complaints of a strong desire to move legs during periods of rest or inactivity, which is relieved by movement (most pronounced in the evening or at night). Multiple studies have reported drug-induced RLS caused by antipsychotics, antidepressants and antiepileptic medications. Risk factors for drug-induced RLS include older age, gastrointestinal diseases, high medication dose, simultaneous use of ≥2 drugs. The mechanism of drug-induced RLS is most often associated with the effect of medications on various receptors and neurotransmitter systems, in particular, the dopamine system. Drug-induced RLS treatment includes identification and withdrawal of a drug that caused RLS or a decrease in its dosage. Prevention of drug-induced RLS is based on compliance with the principles of rational pharmacotherapy.

[Hypertension and insomnia].

Insomnia is frequently detected in patients with arterial hypertension (AH): from 19% to 47.9% of all cases according to epidemiological studies. On the other hand, the frequency of hypertension in patients with insomnia ranges from 21.4% to 50.2%, whereas in patients without insomnia, from 11.0% to 41.8%. In single studies in which patients with insomnia underwent ambulatory blood pressure monitoring (ABPM), these patients showed higher nocturnal blood pressure levels. Recent data suggests that insomnia is also a risk factor for hypertension. Among the pathogenetic mechanisms explaining the relationship between hypertension and insomnia, an increase in the activity of the main neuroendocrine stress systems, sympatho - adrenal and hypothalamic - pituitary - adrenal, and the frequent presence of concomitant anxiety disorders are discussed. To determine the sleep quality in patients with insomnia, the Pittsburgh Sleep Quality Index (PSQI) is most often used, patients with hypertension in a number of studies had higher total PSQI score compared to individuals with normal blood pressure. PSQI score correlates with systolic and diastolic blood pressure level, as well as with the presence of non - dipper blood pressure profile. Both hypertension and insomnia are associated with impaired cognitive functions. However, the relationship between cognitive impairment and insomnia is rather contradictory, which is most associated with the methodology for assessing cognitive functions and differences in the initial clinical and demographic characteristics of the examined patient population.

[Drug-induced glaucoma]. / Lekarstvenno-indutsirovannaya glaukoma.

Glaucoma is seen as a heterogeneous group of diseases characterized by optical neuropathy with associated visual field loss; one of the main risk factors for its development is increased intraocular pressure (IOP). In the case of drug-induced glaucoma (DIG), patients develop elevated IOP, optic neuropathy and visual field defects associated with the use of certain drugs. Corticosteroids are one of the most well-known classes of drugs that can cause an increase in IOP through the open-angle mechanism. Drug-induced glaucoma, which develops similarly to open-angle glaucoma, can also be caused by some non-steroidal anti-inflammatory agents, antibodies to the endothelial growth factor, etc. Classes of drugs that can cause angle-closure glaucoma include topical anticholinergic or sympathomimetic drops, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinsonian drugs, antipsychotic drugs, antispasmodics. Products containing sulfa group drugs can cause DIG due to a different closing angle mechanism involving a forward rotation of the ciliary body. It is important for medical practitioners to be aware of this unwanted drug reaction in order to prevent, detect and treat DIG. In the case of drug-induced increase in IOP, if the underlying disease allows discontinuation of drugs, this measure usually leads to normalization of IOP. In cases when the patient's IOP does not normalize after discontinuation of steroids or when they must continue to take corticosteroids, the administration of topical drugs for the treatment of glaucoma should be considered.

[Treatment of chronic heart failure: is deprescribing possible?]

Deprescribing is a scheduled withdrawal, dose reduction, or replacement of a medicine with a safer one. Several groups of medicinal products (MPs) are used simultaneously in the treatment of chronic heart failure. This increases the risk of adverse drug reactions, particularly in elderly and senile patients. A systematic search for literature allowed evaluating possibilities of deprescribing for the following pharmaceutic groups: 1) MPs influencing the renin-angiotensin-aldosterone system; 2) beta-blockers; 3) digoxin; and 4) diuretics. Three systematic reviews and several studies were analyzed to determine the most feasible and potentially optimal regimens of deprescribing in CHF. It was established that in CHF, deprescribing has a very limited potential for use due to the documented, obvious effect of some MP groups on prediction and severity of clinical symptoms in CHF patients.

[Drug-induced dysphonia]. / Lekarstvenno-indutsirovannaya disfoniya.

Drug-induced dysphonia is a non-life-threatening adverse drug reaction, however, this complication can significantly worsen the quality of life of patients, especially those in voice-speaking professions. The aim of the work was to search for information about the prevalence, etiology, pathogenesis, and features of treatment and prevention of drug-induced dysphonia. In the case of some drugs, the true prevalence may be higher than described in the literature, due to the fact that dysphonia is in most cases mild, reversible and, in comparison with other undesirable drug reactions, rarely attracts the attention of both the patient and practitioners.

[Mechanisms for the Development of Blood Pressure Variability and the Potential of Antihypertensive Drugs in Their Correction].

Blood pressure variability (BPV) is the fluctuations of blood pressure over a certain period of time under the influence of various factors. The issue of increased BPV is of particular clinical importance due to high predictive value of this parameter as a risk factor for fatal and non-fatal cardiovascular, cerebrovascular and renal events. It is proved that in the BPV increasing, the key role is played by impairments in arterial baroreflexes, which, in turn, are mediated by increased vascular stiffness, impact of angiotensin II and the sympathetic nervous system, endothelial dysfunction, nitric oxide deficiency and aging, including the vascular aging. Antihypertensive drugs that targeting largest amount of pathophysiological mechanisms in BPV increasing have a most advantages in correcting excessive pressure fluctuations. In this regard such drugs are perindopril and amlodipine, which can eliminate almost the entire spectrum of increased BPV causes and, therefore, optimally reduce the cardiovascular risk.