Nicotine dependence and neuropsychotic effects of varenicline

Varenicline is a partial agonist of nicotinic acetylcholine receptors for the therapy of nicotine addiction. The efficacy and safety of the use of varenicline in the treatment of nicotine dependence have been demonstrated in clinical trial EAGLES. These studies describe adverse reactions such us mental disorders: depression, suicidal thoughts, suicidal behavior. However, data on the increase in the incidence of these adverse reactions during longer treatment with varenicline was not obtained. In 2016, the FDA has been presented with information about the risk of development the following serious neuropsychiatric adverse reactions on the using of varenicline: depression, manic syndrome, psychosis, hallucinations, delusions, homicidal ideation, aggression, agitation, anxiety, panic, suicidal ideation, attempt of suicide. These adverse reactions were observed in patients with and without psychiatric disorders

MYOPATHY CAUSED BY THE INTERACTION OF COLCHICINE AND STATINS

Myopathy is a life-threatening disease that can be caused, among other things, by the intake of various medications. Despite the fact  that many drug-induced myopathies are well known, however, many  health professionals are not alert to myopathies caused by drug  interactions. Myopathy is a wellknown adverse reaction of statins,  and muscle damage can range from minor muscle pain and  weakness to life-threatening rhabdomyolysis. Colchicine can also  cause myopathy, including rhabdomyolysis. The combination of  colchicine and statins can significantly increase the risk of myopathy  compared with their intake separately. In cases of development of  myopathy in patients receiving colchicine and statins simultaneously, the most common manifestation of drug interaction was muscle  weakness, occurring in almost every case, and in some cases,  muscle weakness was so severe that the patient lost the ability to  move. In a third of cases, the development of muscle weakness was  accompanied by muscular pain, and darkening of urine to tea shade.  One study showed that 40 % of patients received concurrent combinations of drugs that increased the risk of muscle  damage. It is concluded that the simultaneous administration of  colchicine and statins requires an assessment of the “benefit-risk”  ratio, as well as the administration of drugs in minimally effective doses

How to identify a patient with autoinflammatory syndrome: Clinical and diagnostic algorithms

Autoinflammatory syndromes (AISs) are a group of predominantly hereditary diseases associated with the spontaneous uncontrolled production of proinflammatory cytokines. Most diseases are known to have molecular mechanisms and an inheritance pattern. The paper describes major AISs, such as familial Mediterranean fever; cryopyrin-associated periodic syndrome (familial cold urticaria, Muckle – Wells syndrome, CINCA/NOMID syndrome); tumor necrosis factor-α receptor-associated periodic syndrome; hyperimmunoglobulinemia D syndrome; periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome. An inheritance pattern and molecular defects are characterized for each disease. The principles of diagnosis and therapy are described. The role of interleukin-1 blockers in the therapy of AIS is defined. The most important symptoms that can be used to detect the major forms of AIS are identified. The Gaslini score, a special formula using the clinical symptoms to identify patients at high risk for AIS who need genetic typing and those at low risk for AIS, is described. A clinical diagnostic algorithm is presented, which can be used to detect patients with AIS and to determine indications to and the time of molecular genetic typing, and to choose priority genes

Как распознать пациента с аутовоспалительным синдромом: клинико-диагностические алгоритмы

Autoinflammatory syndromes (AISs) are a group of predominantly hereditary diseases associated with the spontaneous uncontrolled production of proinflammatory cytokines. Most diseases are known to have molecular mechanisms and an inheritance pattern. The paper describes major AISs, such as familial Mediterranean fever; cryopyrin-associated periodic syndrome (familial cold urticaria, Muckle – Wells syndrome, CINCA/NOMID syndrome); tumor necrosis factor-α receptor-associated periodic syndrome; hyperimmunoglobulinemia D syndrome; periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome. An inheritance pattern and molecular defects are characterized for each disease. The principles of diagnosis and therapy are described. The role of interleukin-1 blockers in the therapy of AIS is defined. The most important symptoms that can be used to detect the major forms of AIS are identified. The Gaslini score, a special formula using the clinical symptoms to identify patients at high risk for AIS who need genetic typing and those at low risk for AIS, is described. A clinical diagnostic algorithm is presented, which can be used to detect patients with AIS and to determine indications to and the time of molecular genetic typing, and to choose priority genes.Аутовоспалительные синдромы (АВС) – группа преимущественно наследственных заболеваний, связанных со спонтанной неконтролируемой продукцией провоспалительных цитокинов. Для большинства заболеваний известны молекулярные механизмы и тип наследования. Представлено описание основных АВС, таких как семейная средиземноморская лихорадка, криопирин-ассоциированный периодический синдром (семейная холодовая крапивница, синдром Muckle – Wells, синдром CINCA/NOMID), периодический синдром, связанный с мутацией в гене рецептора фактора некроза опухоли (ФНО) α, синдром гипериммуноглобулинемии D, синдром периодической лихорадки с аденитом, фарингитом и афтозным стоматитом. Для каждого заболевания даны характеристика типа наследования, молекулярный дефект. Описаны принципы диагностики и терапии. Определена роль блокаторов интерлейкина 1 в терапии АВС. Выделены важнейшие симптомы, при помощи которых можно распознать основные формы АВС. Приведена Gaslini score – специальная формула, позволяющая на основании клинических симптомов выделить пациентов с высоко вероятным АВС, которым необходимо генетическое типирование, и пациентов, у которых вероятность АВС невелика. Представлен клинико-диагностический алгоритм, с помощью которого можно распознать пациентов с АВС без отчетливой клинической картины и определить показания и сроки выполнения молекулярно-генетического типирования, выбрать приоритетные гены

Эффективность адалимумаба при хроническом переднем увеите, ассоциированном с ювенильным идиопатическим артритом и резистентным к терапии метотрексатом: ретроспективное исследование серии случаев

Background: Juvenile idiopathic arthritis (JIA) associated uveitis may be the cause of not only visual acuity decrement, but also blindness. At the same time, in some patients therapy with methotrexate can not prevent the development of these complications.Objective: Our aim was to investigate the efficiency and safety of using a tumor necrosis factor inhibitor (adalimumab) in patients with JIA-associated uveitis.Methods: We conducted a retrospective single-arm study of a series of cases. The results of using adalimumab were evaluated in patients with JIA-associated chronic anterior uveitis, who have been under observation for no less than 1 year before and after starting using adalimumab. The latter was prescribed due to progressing and/or recidivous methotrexate-resistant uveitis.Results: We have analyzed clinical case records of 36 children with JIA-associated uveitis. At the start of therapy with adalimumab, actual uveitis was diagnosed in 30 (83%) patients. Remission was achieved in 29 of 30 cases in 2 (2; 12) weeks in patients with actual uveitis. 11 (31%) patients had a uveitis exacerbation 28 (13; 69) weeks after adalimumab therapy started. Adalimumab reduced the exacerbation frequency from 4 (1; 9) to 0 (0; 1) exacerbations per year for one patient (p < 0,001), and reduced the proportion of patients who were treated with topical glucocorticosteroids (from 83 to 8%). There were no differences (in achieving remission and reducing exacerbation frequency) with regard to patients’ sex, involvement of one or both eyes in the disease onset, antinuclear factor seropositiveness, uveitis type and character of joints affection.Conclusion: Adalimumab promotes fast and long-lasting remission of JIA-associated methotrexate-resistant uveitis.Увеит, ассоциированный с ювенильным идиопатическим артритом (ЮИА), может быть причиной не только снижения остроты зрения, но и слепоты. При этом у некоторых больных терапия метотрексатом не позволяет предупредить развитие этих осложнений.Цель исследования: изучить эффективность и безопасность применения ингибитора фактора некроза опухоли адалимумаба у пациентов с ЮИА-ассоциированным увеитом.Методы. Проведено ретроспективное неконтролируемое исследование серии случаев. Результаты применения адалимумаба оценивали у пациентов с ЮИА-ассоциированным хроническим передним увеитом, которых наблюдали не менее 1 года до и после начала применения адалимумаба. Препарат назначали по причине прогрессирующего и/или рецидивирующего течения увеита, резистентного к терапии метотрексатом.Результаты. Осуществлен анализ историй болезни 36 детей с ЮИА-ассоциированным увеитом. Активный увеит на момент начала терапии адалимумабом был диагностирован у 30 (83%) пациентов. У пациентов с активным увеитом ремиссия была достигнута в 29 из 30 случаев через 2 (2; 12) нед. Обострение увеита развилось у 11 (31%) пациентов через 28 (13; 69) нед от начала терапии адалиму- мабом. Применение адалимумаба привело к снижению частоты обострений с 4 (1; 9) до 0 (0; 1) случаев в год на одного пациента (р < 0,001), уменьшению доли пациентов, получавших местные глюкокортикостероиды (с 83 до 8%). Не обнаружено различий в достижении ремиссии и снижении частоты обострений в зависимости от пола пациентов, вовлечения в дебюте болезни одного или обоих глаз, серопозитивности по антинуклеарному фактору, типа увеита, характера суставного поражения.Заключение. Адалимумаб способствует достижению быстрой и продолжительной ремиссии ЮИА-ассоциированного увеита, резистентного к терапии метотрексатом

Personality profiles and the "russian soul": Literary and scholarly views evaluated

Many domestic and foreign observers have claimed that Russians have a unique constellation of personality traits that mirrors their distinctive historical and cultural experience. To examine the hypothesized uniqueness of Russian personality, members of the Russian Character and Personality Survey collected data from 39 samples in 33 administrative areas of the Russian Federation. Respondents (N = 7,065) identified an ethnically Russian adult or college-aged man or woman whom they knew well and rated the target using the Russian observer-rating version of the Revised NEO Personality Inventory. The mean personality profile of Russians was very similar to the international average based on 50 different countries, debunking the myth of a unique Russian soul.The small variations from world norms did not converge with depictions of Russian national character in fiction and the scholarly literature. New items intended to capture distinctive, emic aspects of Russian personality provided no new information beyond the familiar Big Five dimensions. Religion, ethnicity, and beliefs about the uniqueness of the Russian character and the malleability of personality traits had little effect on personality ratings. Perceptions of the Russian soul do not seem to be based on the personality traits of Russians

Тяжелые грибковые инфекции у детей с ревматическими заболеваниями

Introduction. In children with rheumatic diseases, severe fungal infections (invasive mycoses – IM) are not well understood.Objectives. To analyze risk factors, disease course of IM in children with systemic rheumatic diseases.Materials and methods. For diagnosis of IM were used criteria EORTC/MSGERC, 2019. We reviewed the literature over the past 15 years on IM in children with rheumatic diseases from the international databases Pubmed and Web of Science.Results. In retrospective multicenter study were included 8 children with IM and systemic rheumatic diseases: ANCA-associated vasculitis (n=4), systemic lupus erythematosus (n=3), juvenile rheumatoid arthritis (n=1). Median age was 13,5 (8-17) y., boys – 67%. Invasive aspergillosis was diagnosed in 5 patients and invasive candidiasis – 3. The risk factors of invasive mycoses were high rheumatic disease activity (100%), corticosteroids (prednisolone ≥ 0,3 mg/kg/d) use for ≥21 d (87,5%), immunosuppressive therapy (87,5%), recent (≤ 2 weeks) pulse steroid therapy (75%), hemophagocytic lymphohistiocytosis (62,5%), prolonged (≥ 10 days) severe neutropenia (≤ 0,5х109/l) (62,5%), and prolonged (≥10 days lymphopenia (≤ 1,0х109/l) (37,5%). In patients with invasive aspergillosis the involved organ was the lung, in patients with invasive candidiasis a candidemia was diagnoses. All patients received antifungal therapy. The overall 30 days survival rate was 37,5%.Сonclusions. Children with high rheumatic diseases activity and intensive treatment with immunosuppressive agents should be considered as patients with a high risk of invasive mycoses with a high mortality. Введение. У детей с ревматическими заболеваниями тяжелые грибковые инфекции (инвазивные микозы) изучены недостаточно.Цель. Проанализировать факторы риска, клинические проявления и результаты лечения инвазивных микозов у детей с ревматическими заболеваниями.Материалы и методы. Диагностику и оценку результатов лечения инвазивных микозов проводили на основании критериев EORTC/MSGERS, 2019. Провели обзор литературы из международных баз данных Pubmed и Web of Science за последние 15 лет.Результаты. При ретроспективном мноогоцентровом исследовании выявили 8 детей с ИМ и ревматическими заболеваниями: АНЦА-ассоциированный васкулит (n=4), системная красная волчанка (n=3), ювенильный ревматоидный артрит (n=1). Медиана возраста составила 13,5 лет (8–17), мальчики – 67%. Инвазивный аспергиллез диагностировали у 5 пациентов, инвазивный кандидоз – у 3. Установлены факторы риска развития инвазивных микозов: высокая активность ревматологического заболевания (100%), применение системных глюкокортикостероидов (преднизолон ≥ 0,3 мг/кг/сут) более 21 дня (87,5%), применение иммунодепрессантов (87,5%), недавняя (≤ 2 недель) пульс-терапия системными глюкокортикостероидами (75%), гемофагоцитарный синдром (62,5%), выраженная нейтропения (≤ 0,5×109 /л) более 10 дней (62,5%), лимфоцитопения (≤1,0×109 /л) более 10 дней (37,5%). При инвазивном аспергиллезе у всех пациентов выявили поражение легких, при инвазивном кандидозе – кандидемию. Антифунгальную терапию получали 100% пациентов. Общая выживаемость больных в течение 30 дней от диагностики ИМ составила 37,5%.Вывод. Детей с высокой активностью ревматических заболеваний и интенсивной иммуносупрессивной терапией следует отнести к группе риска развития ИМ с возможной высокой летальностью.

Poetic Classics from the Viewpoint of Contemporaneity: The Image of "Devilish laughter" in A. Tvardovsky's Poems

Relying on Bakhtin's concept of the "liberating laughter" and Sergei Averintsev's notion of "the devil's laughter," the article undertakes an attempt (as called 264 forth under the present conditions of humanist consciousness) to bring to light a peculiar destructive and provocative form of laughter in Tvardovsky's poetic universe. It would seem that such a mode of laughter could not exist in Tvardovsky's poetry. Yet, focusing on Tvardovsky's long poems, the author discovers that the image of "devilish laughter ", though a rare, "extreme" occurrence in the poet's world, is nevertheless present and significant

Social media as a source of information on drug safety and how to extract it

We have prepared this review of the domestic and foreign scientific literature on how to use the social media for pharmacovigilance purposes. We examined the complexities that are connected with this kind of monitoring and how to extract information on adverse drug reactions from the Internet. The importance of a systematic approach in assessing the safety of drugs and the benefits of social networks is underlined. A description of applications for smartphones, which allow you to easily and quickly report drug adverse reactions is provided