Drugs influencing on PCSK9 activity: modelling of efficacy in patients who had myocardial infarction with uncontrolled dyslipidemia

Cardiovascular diseases are the leading cause of death worldwide. It is possible to influence the development of these diseases by influencing their main pathogenetic link — dyslipidemia.Aim: to evaluate, using the example of alirocumab, the potential effect of drugs affecting the activity of PCSK9 on the achievement of goals for the prevention of the development of cardiovascular diseases and cardiovascular complications in patients of working age who had an acute myocardial infarction (MI) less than a year ago, with uncontrolled dyslipidemia.Materials and methods. The target group was created based on the Russian clinical guidelines; its number was calculated using Russian registry data. Based on the published results of the clinical trial of alirocumab ODYSSEY OUTCOMES in a group of patients with LDL cholesterol levels of more than 2.6 mmol/l (100 mg/dl), a model was built to estimate the number of fatal and non-fatal outcomes in the target group with standard therapy and with alirocumab.Results. The effect of alirocumab administration was modeled in patients of working age who had a myocardial infarction less than 12 months ago with an LDL cholesterol level of more than 5.0 mmol/l, the number of this group in the Russian Federation was estimated to be 3,029 people. It has been shown that with therapy in this group, mortality can be reduced by 29%, and the number of non-fatal cardiovascular events — by 22%, i. e. alirocumab therapy in this group for 2 years can prevent 29 deaths and 185 non-fatal events, with an increase in the duration of therapy to 5 years, the number of lives saved will be 117 and 401 non-fatal cardiovascular events will be prevented.Conclusion. Modeling has shown that alirocumab therapy in patients with recent myocardial infarction and LDL cholesterol levels above 5.0 mmol/L will significantly reduce mortality in this group and prevent the development of serious nonfatal cardiovascular complications, which will also reduce the burden on specialized hospitals, as well as prevent patients from becoming disabled. At the same time, decision making requires a balanced consideration of all ethical, clinical and economic aspects, including the assessment of costs and potential effects from the position of the of a willingness to pay and the formation of the budget of the health system

Survival of drug resistant tuberculosis patients in Lithuania: retrospective national cohort study

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement FP7-223681.

PREVALENCE OF HIGH CARCINOGENIC RISK HUMAN PAPILLOMAVIRUS IN THE REPUBLIC OF SAKHA (YAKUTIA), ST. PETERSBURG AND THE REPUBLIC OF KARELIA

Results of the study in three regions of the Russian Federation have shown widespread of high carcinogenic human papillomavirus among patients of dermatovenerological and gynecological profile. Detection of viral DNA in the material from the cervix and urethra ranged from 25,2 (Karelia) to 42,5 (Sakha Republic (Yakutia) per 100 examined patients. In all areas in 2010-2011 first place was occupied by 16-th virus genotype - from 11,5 (Sakha Republic (Yakutia) to 15,9 (St. Petersburg) per 100 patients. Prevalence of 11 other types differs. In the Sakha Republic (Yakutia) the second rank place was occupied by types 31 and. 51 (8,0 per 100 examined patients), in St. Petersburg - by 56 and 31 types (9,7 and. 7,6 per 100 patients). Age risk group contains patients of the age of 20-29 years. Information on circulating genotypes of the virus is a necessary part of surveillance to validate vaccination against human papillomavirus infection and evaluation of its efficiency

Assessing natural herd immunity to tick-borne encephalitis in Republic Sakha (Yakutia)

Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection vastly spread in the mid-latitude climate zone of theEurasia. Lethal cases and disability related to TBE determine its high epidemiological significance as well as underlie undiminished attention to prevent it in endemic territories. At the same time, TBE epidemiologic features significantly differ in various geographic areas. Importantly, Republic Sakha (Yakutia) is not among TBE endemic areas in theRussian Federation. However, in the last decade an increased incidence of ixodic tick bites was registered in the Republic Sakha. A pattern of pathogen-specific population immunity is one of the most valuable criteria for assessing magnitude of epidemic process in TBE foci. Hence, our study was aimed at assessing natural herd immunity TBEV in Republic Sakha associated with elevated incidence of tick bite visits. Here, we analyzed the data regarding the rate of tick attacks in the period of 2001–2007 in Republic Sakha. Residents and individuals unvaccinated against TBEV in the city ofYakutskas well as various administrative regions were examined to record the peak incidence of tick attacks. It was found that a range of the administrative regions recording with registered of ixodic tick attacks and elevated incidence of tick bites was expanded. Moreover, the top incidence of tick bites was annually recorded in the south regions of the republic Aldanian, Neryungri, Olyekminsk, Leninsk, Khangalassky districts, city ofYakutskand its suburbs. Furthermore, TBEV-specific immunoglobulins were detected in 5.7±0.68% of the residents examined suggesting about contacts with the pathogen. In addition, the peak count of seropositive people (8.9±1.85%) was identified in Namsky district located in the central part of the republic. Overall, detection rate of TBEV-specific antibodies among general adult population (6.9±0.95%) was significantly higher compared to those observed in children (3.9±0.89%, р < 0.05). no significant differences in urban (5.8±1.12%) vs. rural population (5.63±0.84%) was found

ПРИНЦИПИАЛЬНОЕ РАЗЛИЧИЕ МЕТОДОВ НИЗКОЧАСТОТНОГО И УЛЬТРАЗВУКОВОГО ВОЗДЕЙСТВИЙ НА РАСПЛАВЫ

There were considered factors that determine difference of low and ultrasonic frequency treatment methods with regard to composite melts: cavitation events, dissipation losses, capability to turbulent mixing of melt. There was proven independence of every of these methods.Рассматриваются факторы, определяющие различие низкочастотного и ультразвукового методов обработки композиционных расплавов: кавитационные явления, диссипативные потери, способность к турбулентному перемешиванию расплава. Доказывается самостоятельность каждого из методов

Организационно-экономические аспекты применения триплетов в терапии рецидивирующей и рефрактерной множественной миеломы в условиях российского здравоохранения

Background. The introduction of innovative drugs has significantly increased the treatment effectiveness in patients with relapsed/refractory multiple myeloma (RRMM), but the question of whether these expensive options can be financially secured remains open.Objective: to assess the cost of triplets of targeted drugs ixazomib, carfilzomib, elotuzumab and daratumumab with lenalidomide and dexamethasone used in the treatment of RRMM, and to determine possible payment options for this therapy at the level of the Russian Federation subjects.Material and methods. The cost of an annual course of treatment with the studied regimens with centralized purchases and the cost of targeted drugs per hospitalization case were calculated based on the maximum registered prices, recommended doses and treatment regimens. The normative legal acts regulating the payment of drug therapy for multiple myeloma were analyzed and possible financing channels and their limitations were identified. Using the example of the Volgograd and Saratov Regions, tariffs under the compulsory medical insurance system were calculated and their sufficiency in covering the cost of targeted therapy was estimated.Results. The cost of an annual course of triplet therapy per patient in the case of centralized procurement of drugs ranged from 5.51 million rubles (regimen with ixazomib) up to 8.03 million rubles (regimen with carfilzomib). The cost per hospitalization, depending on the number of doses, ranged from 80,667–242,000 rubles (ixazomib, 1–3 doses) in the Saratov Region up to 239,618–958,472 rubles (daratumumab, 1–4 doses) in the Volgograd Region. Possible reimbursement channels are High-Cost Nosologies (HCN), Obligatory Medical Insurance (OMI) and Regional Drug Coverage (RDC) programs, nevertheless triplet therapy cannot be purchased via the single channel and the combination of them is required. It has been shown that, in most cases, the costs for a case of targeted drug treatment in studied regions are covered by the average tariff for the corresponding diagnosis-related group (DRG), except for cases with a maximum duration in a day hospital setting. An analysis of the RDC lists and the procurement of drugs in the studied regimens at the expense of regional budgets showed that lenalidomide, ixazomib, carfilzomib, elotuzumab and daratumumab are included in the restrictive list in regions 77, 74, 66, 63 and 47, but they are purchased only in regions 15, 24, 6, 4 and 6, respectively.Conclusion. The use of a triplet with ixazomib is characterized by the lowest costs, which indicates its greater economic attractiveness relative to carfilzomib, daratumumab and elotuzumab in the treatment of patients with RRMM. The tariffs established in the current DRG model retain the possibility of paying for treatment with the high-cost medicines at the expense of the OMI funds in combination with the HCN or RDC programs. There are reasons to believe that the expansion of the list of 14 HCN program will increase the provision of patients with highly effective therapy and also reduce the financial burden on the regions.Актуальность. Появление инновационных лекарственных препаратов позволило значительно повысить эффективность лечения пациентов с рецидивирующей и рефрактерной множественной миеломой (РРММ), однако остается открытым вопрос о возможности финансового обеспечения этих дорогостоящих опций.Цель: провести оценку стоимости триплетов таргетных препаратов иксазомиб, карфилзомиб, элотузумаб и даратумумаб с леналидомидом и дексаметазоном, используемых в терапии РРММ, и определить возможные варианты оплаты данной терапии на уровне субъекта Российской Федерации.Материал и методы. Рассчитаны стоимость годового курса терапии исследуемыми схемами при централизованных закупках и стоимость таргетных препаратов в расчете на 1 случай госпитализации на основании предельных зарегистрированных цен, рекомендуемых дозировок и схем назначения. Проанализированы нормативные правовые акты, регулирующие оплату лекарственной терапии при множественной миеломе, определены возможные каналы финансирования и их ограничения. На примере Волгоградской и Саратовской областей рассчитаны тарифы для оплаты в системе обязательного медицинского страхования (ОМС) и оценена их достаточность для покрытия стоимости таргетной терапии.Результаты. Стоимость годового курса терапии пациента триплетами в случае централизованных закупок препаратов колебалась от 5,51 млн руб. (схема с иксазомибом) до 8,03 млн руб. (схема с карфилзомибом). Стоимость в расчете на 1 госпитализацию в зависимости от числа введений составила от 80 667 – 242 000 руб. (иксазомиб, 1–3 введения) в Саратовской области до 239 618 – 958 472 руб. (даратумумаб, 1–4 введения) в Волгоградской области. Возможными источниками финансирования являются программы ОМС, высокозатратных нозологий (ВЗН) и регионального льготного обеспечения (РЛО), но при этом в настоящий момент терапия триплетами не может быть оплачена из одного источника, необходима их комбинация. Показано, что в большинстве ситуаций затраты на 1 случай лечения таргетными препаратами в выбранных субъектах покрываются средним тарифом на соответствующую клинико-статистическую группу (КСГ), за исключением случаев с максимальной длительностью в условиях дневного стационара. Анализ перечней РЛО и закупок препаратов исследуемых схем за счет средств региональных бюджетов показал, что леналидомид, иксазомиб, карфилзомиб, элотузумаб и даратумумаб включены в ограничительный перечень в 77, 74, 66, 63 и 47 регионах соответственно, однако закупаются только в 15, 24, 6, 4 и 6 регионах соответственно.Заключение. Применение триплета с иксазомибом характеризуется наименьшими затратами, что свидетельствует о его большей экономической привлекательности относительно карфилзомиба, даратумумаба и элотузумаба в терапии пациентов с РРММ. Установленные в действующей модели КСГ тарифы сохраняют возможности оплаты лечения с применением дорогостоящих препаратов за счет средств ОМС в комбинации с программами ВЗН или РЛО. Есть основания полагать, что расширение перечня программы 14 ВЗН позволит повысить обеспеченность пациентов высокоэффективной терапией, а также снизить финансовую нагрузку на регионы

Моделирование влияния ферментозаместительной терапии на развитие жизнеугрожающих исходов у пациентов с болезнью Фабри

Fabry disease (FD) is a severe lysosome storage disease caused by congenital deficiency of the enzyme α-galactosidase A and characterized by the risk of renal failure combined with cardiovascular and CNS complications. According to the currently available information, the early start of enzyme replacement therapy (ERT) leads to a significant improvement in patient’s condition.The aim of the study is to assess whether the timely ERT prevents severe FD complications and to calculate the number of prevented cases as depending on the time of ERT start.Materials and methods. The proposed model is based on the published results on patients with FD, receiving agalsidase alpha as ERT (no data for agalsidase beta was found). The expected number of cases with life-threatening complications was calculated for different starting timepoints and durations of the ERT.Results. In patients with FD, continuous ERT during five years reduces the number of serious cardiovascular and renal complications by 25%. An early start of ERT makes it possible to additionally (as compared with a late start) prevent the complications in more than 20% of cases.Conclusion. The early initiation of RPT in patients with FD can significantly reduce the occurrence of severe lifethreatening complications, increase the patients’ survival and improve their quality of life. Болезнь Фабри (БФ) – тяжелое орфанное прогрессирующее наследственное заболевание из группы лизосомных болезней накопления, характеризующееся риском развития почечной недостаточности и тяжелых осложнений со стороны сердечно-сосудистой и центральной нервной систем, причиной которого является врожденный дефицит фермента α-галактозидазы А. По имеющимся на настоящий момент сведениям, раннее назначение препаратов ферментозаместительной терапии (ФЗТ) приводит к значительному улучшению исходов для пациентов.Цель исследования – оценить число предотвращенных случаев тяжелых осложнений БФ в зависимости от наличия ФЗТ и времени ее начала.Материалы и методы. В модели, построенной на основании опубликованных результатов длительного наблюдения за пациентами с БФ, получающими в качестве ФЗТ агалсидазу альфа (аналогичных данных для агалсидазы бета найдено не было), было рассчитано ожидаемое число случаев развития жизнеугрожающих осложнений в зависимости от сроков назначения и длительности проведения ФЗТ.Результаты. Проведение ФЗТ у пациентов с БФ в течение пяти лет позволяет сократить на 25% число тяжелых осложнений со стороны сердечно-сосудистой системы и почек. Раннее начало ФЗТ позволяет дополнительно (по сравнению с более поздним началом) предотвратить осложнения более чем в 20% случаев.Заключение. Раннее начало ФЗТ у пациентов с БФ позволяет существенно замедлить развитие у них тяжелых, жизнеугрожающих осложнений, увеличить продолжительность и повысить качество их жизни.

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Background. To date, there are many pharmacogenetic algorithms for selecting the dose of warfarin. However, there is very little information about the predictive accuracy of the algorithms. We decided to evaluate the predictive accuracy of the Gage algorithm, using a calculator, located on the web site (http://www.warfarindosing.org) in two ethnic groups (Caucasians and Asians), living in Russia.Aim. To compare the actual warfarin dose (AWD) to the calculated warfarin dose (CWD), using the algorithm in two ethnic groups taking warfarin.Materials and methods. We included 114 patients (66 Caucasians and 48 Asians): the mean age was60.91 ± 12.34 years; 61 (53.51 %) men, and 53 (46.49 %) women. The comparative characteristics of the algorithm were tested using the mean absolute error (MAE) between AWD and CWD, and percentage of patients, whose CWD fell within 20 % of AWD (percentage within 20 %). Genotyping for CYP2C9*2, CYP2C9*3, CYP4F*2 and VKORC1 was performed by real-time polymerase chain reaction (RT-PCR) method using Pharmacogenetics Warfarin reagent kits (DNA technology, Russia).Results. The Gage algorithm produced the predictive accuracy with MAE = 1.02 ± 0.16 mg/day and percentage within 20 % for Asian patients was 39.6 %. We obtained MAE = 1.33 ± 0.16 mg/day and percentage within 20 % for Caucasian patients was 40.9 %. In two ethnic groups (Caucasians and Asians) of the Russian population, overall performance of warfarin pharmacogenetic dosing by the Gage algorithm was similar.Conclusions. Despite the performance limitation of the current warfarin pharmacogenetic dosing Gage algorithm, constant international normalized ratio monitoring is important