НОВЫЕ ГИБРИДНЫЕ МАТЕРИАЛЫ ДЛЯ ОРГАНИЧЕСКИХ СВЕТОИЗЛУЧАЮЩИХ ДИОДНЫХ УСТРОЙСТВ

We studied regularities of polymorphous transitions in high−purity powder preparations of metal complex of 8−hydroxyquinoline with aluminum, gallium and indium (Meq3, where Me= Al, Ga, In) in the 300−712 K temperature range. According to the results of luminescent and Raman spectra measurements combined with XRD analysis, the general pattern of the polymorphous transitions in all the investigated compounds is β → α→ δ→ γ → ε. Hybrid materials (HM) were synthesized based on borate glass matrix with 0.02–0.1 wt % Meq3. Bulk samples were obtained by melting, and HM thin films were produced by high vacuum deposition. The luminescent properties of the hybrid materials were studied at room temperature. For the bulk HM an increase in the synthesis duration resulted in the shift of the maximum luminescence peak towards short wavelengths relative to that of pure δ(γ)−Meq3 by 40 nm for Alq3, 15 nm for Gaq3, and 10 nm for Inq3.Изучены закономерности полиморфизма в высокочистых кристаллических три−(8−оксихинолятах) алюминия, галлия и индия (Meq3) в интервале температур от 300 до 712 К. По результатам анализа спектров фотолюминесценции, спектров комбинационного рассеяния света и рентгенофазового анализа построена обобщенная картина, согласно которой последовательность полиморфных переходов для всех изученных соединений одинакова: β → α → δ → γ → ε. На основе высокочистых однофазных препаратов изученных металлокомплексов и оксида бора синтезированы новые гибридные материалы: объемные образцы (методом сплавления), тонкие пленки (вакуумным термическим испарением). Изучены фото− и электролюминесцентные свойства гибридных материалов при комнатной температуре. Установлено, что для объемных гибридных материалов увеличение времени синтеза c 5 до 60 мин приводит к смещению максимума спектра фотолюминесценции от значения, характерного для чистого δ(γ)−Meq3 в коротковолновую область спектра на 40 нм для Alq3, 15 нм для Gaq3 и 10 нм для Inq3

Эффективность комбинации глекапревир/пибрентасвир у пациентов с хроническим гепатитом С, вызванным вирусами генотипов 1–6, в рутинной клинической практике в России

Background: Glecaprevir/pibrentasvir (GLE/PIB) is the first pangenotypic ribavirin-free regimen allowing for treatment duration as short as 8 weeks for the majority of patients with chronic hepatitis C (CHC) genotypes (GT) 1 to 6. The results of clinical trials showed good tolerability of GLE/PIB and high virologic response rate (mostly >95%) among different patient populations. The main objective of this study was to determine how the efficacy and safety of GLE/PIB translates into real-world clinical settings in Russia.Materials and Methods: This was a prospective, multicenter observational study in patients with CHC who received the GLE/PIB regimen. The treatment regimen was prescribed by a physician in accordance with all applicable requirements before the enrollment in the study. Patients were observed for the duration of GLE/PIB therapy and at least for up to 12 weeks after the treatment completion. Real-world data were collected in patient records. Follow-up visits, procedures, and diagnostic methods followed physicians’ routine clinical practice.Results: Overall 161 patients were enrolled in the study in 11 study sites of them 128 patients had sufficient follow-up data to assess sustained virological response 12 weeks [i.e. ≥70 days] after the end of treatment with GLE/PIB (SVR12). Overall, 127 out of 128 patients (99.2%) achieved SVR12. Depending on treatment duration the following SVR12 rates were achieved: 98.7% in 8-week group (75/76), 100% in 12-week group (49/49) and 100% in 16-week group (3/3). One patient failed to achieve SVR, the exact reasons of failure couldn’t be established by the Investigator.Since only one patient didn’t achieve primary endpoint the following SVR12 rates were achieved in different subpopulations: 91.7% in patients with GT2 (11/12); 98.9% in non-cirrhotic patients (88/89); 99.1% in treatment-naïve patients (113/114); 99.1% in patients without HIV co-infection (116/117); 99.2% in patients younger than 65 years (120/121).On the other hand, SVR12 was achieved by all patients (100%) in the following subpopulations: patients with GT3 (n=76), GT1a (n=5), GT1b (n=29) and other GTs (n=6); cirrhotic patients (n=36) and those with unknown cirrhosis status (n=3); treatment-experienced patients (n=14); HIV/HCV co-infected patients (n=11); patients older than 65 years (n=7); and drug users (n=10).No clinically significant abnormalities in the key laboratory parameters were noted during the study. On contrary, the overall improvement of the liver enzymes was observed at SVR12 Visit. There were 3 patients with 3 adverse events (AEs): 2 cases were mild (cough and rash), and 1 case was severe and evaluated as a serious AE (hepatic decompensation). Hepatic decompensation led to the patient withdrawal from the study; this serious AE was preceded by 2 months of daily alcohol consumption and in the investigator’s opinion was not related to GLE/PIB intake. Of all AEs only rash was related to GLE/PIB administration according to investigator’s opinion.Conclusion: GLE/PIB has proven to be a highly effective treatment regimen in the routine clinical practice in patients with all hepatitis C virus genotypes, including those with GT3 and compensated liver cirrhosis. SVR12 rates demonstrated in this study are fully consistent with the previously published data. The regimen was well tolerated by patients.Цель: комбинация глекапревира и пибрентасвира – это первая пангенотипипная схема терапии хронического гепатита С, не требующая добавления рибавирина и позволяющая проводить 8-недельную терапию у большинства пациентов с хроническим гепатитом С и генотипами 1–6. Результаты клинических исследований показали хорошую переносимость комбинации глекапревира и пибрентасвира и высокую частоту достижения вирусологического ответа (>95%) в различных группах пациентов. Основной целью настоящего исследования стала оценка эффективности и безопасности комбинации глекапревира и пибрентасвира в условиях реальной клинической практики в России.Материалы и методы: данное проспективное многоцентровое наблюдательное исследование было проведено у пациентов с хроническим гепатитом С, получавших комбинацию глекапревира и пибрентасвира. Терапия назначалась лечащим врачом в соответствии со всеми применимыми требованиями до включения пациента в исследование. Наблюдение за пациентами осуществлялось на протяжении терапии комбинацией глекапревира и пибрентасвира и по меньшей мере в течение 12 недель после ее завершения. Информация собиралась из медицинских записей пациентов. Визиты, процедуры и диагностические манипуляции проводились в соответствии с принятой рутинной клинической практикой.Результаты: в 11 центрах в исследование был включен 161 пациент, из них у 128 пациентов были собраны достаточные сведения для оценки устойчивого вирусологического ответа через 12 недель (т.е. ≥70 дней) после окончания терапии комбинацией глекапревира и пибрентасвира. В общей сложности у 127 из 128 пациентов (99,2%) был достигнут устойчивый вирусологичес кий ответ через 12 недель. В зависимости от длительности терапии комбинацией глекапревира и пибрентасвира частота устойчивого вирусологического ответа через 12 недель в различных группах была следующей: 8 недель – 98,7% (75/76), 12 недель – 100% (49/49) и 16 недель – 100% (3/3). У 1 пациента не удалось достичь устойчивого вирусологического ответа через 12 недель, точные причины неудачи не были установлены.Поскольку 1 пациент не достиг первичной конечной точки, в подгруппах пациентов, к которым он принадлежал, была установлена следующая частота достижения устойчивого вирусологического ответа через 12 недель: 91,7% среди пациентов с генотипом 2 (11/12); 98,9% среди пациентов без цирроза (88/89); 99,1% среди ранее не леченных пациентов (113/114); 99,1% среди пациентов без вируса иммунодефицита человека (116/117); 99,2% среди пациентов младше 65 лет (120/121) и 99,2% среди не употреблявших наркотики пациентов (117/118).С другой стороны, устойчивый вирусологический ответ через 12 недель был зарегистрирован у всех пациентов (100%) в следующих подгруппах: пациенты с генотипом 3 (n=76), генотипом 1a (n=5), генотипом 1b (n=29) и «другими» генотипами (n=6); пациенты с циррозом печени (n=36) и с неизвестными данными о циррозе (n=3); пациенты, получавшие противовирусную терапию ранее (n=14); пациенты с ко-инфекцией вируса иммунодефицита человека / вируса гепатита С (n=11); пациенты старше 65 лет (n=7) и пациенты, употреблявшие наркотики (n=10).Клинически значимых отклонений основных лабораторных показателей в ходе исследования не было выявлено. Напротив, отмечено общее улучшение показателей печеночных ферментов на визите устойчивого вирусологического ответа через 12 недель. Зарегистрировано 3 нежелательных явления у 3 пациентов: 2 случая легкой степени тяжести (кашель и сыпь) и 1 тяжелый случай, расцененный как серьезное нежелательное явление (декомпенсация цирроза). Декомпенсация цирроза привела к выбыванию пациента из исследования. По мнению исследователя, данное серьезное нежелательное явление не было связано с приемом комбинации глекапревира и пибрентасвира, его развитию предшествовали 2 месяца ежедневного употребления алкоголя. Из всех нежелательных явлений, по мнению исследователей, только для сыпи была выявлена связь с применением комбинации глекапревира и пибрентасвира.Заключение: доказана высокая эффективность терапии комбинации глекапревира и пибрентасвира в рутинной клинической практике у пациентов со всеми генотипами вируса гепатита С, включая пациентов с генотипом 3 и компенсированным циррозом печени. Частота достижения устойчивого вирусологического ответа через 12 недель, продемонстрированная в этом исследовании, полностью согласуется с ранее опубликованными данными. Режим терапии хорошо переносился пациентами

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

The modern options of chronic hepatitis C antiviral therapy with daclatasvir: results of named patient program

Introduction. The options of antiviral therapy (AVT) in the stages of severe liver fibrosis and cirrhosis (LC) as well as in the patients with comorbidities for the long time were limited to the standard therapy by pegilated interferon (peg-IFN) in combination to ribavirin (RBV). Before official registration of interferon-free treatment modes in 2015 experience of the application was limited to clinical trials or treatment within early approach programs. Aim of investigation. To analyze the efficacy of PTV for chronic hepatitis C within the named patient program of expanded access to daclatasvir. Material and methods. Approval of Ministry of Healthcare of the Russian Federation to import of drugs was received for the treatment of 101 HCV-infected patients with compensated LC, who, been untreated had an urgent need for effective therapy, with estimated life expectancy less than 12 months, in 12 centers of the Russian Federation. The patients with 1b HCV genotype received treatment by combination of daclatasvir and asunaprevir 100 mg, patients with 2 and 3 HCV genotypes, and those with 1b HCV genotype after the liver transplantation received daclatasvir to sofosbuvir combination. Results. Sustained virologic response for 24 wks (SVR24) in early approach program was 89% (83 of 93) of patients with severe liver disease who urgently needed effective treatment with estimated life expectancy of less than 12 months if been untreated. In group of the patients receiving treatment mode of daclatasvir + asunaprevir the frequency of SVR24 achievement was 90%. Of 93 patients who underwent complete treatment course no severe adverse effects were registered. During treatment infrequent nonspecific adverse events, such as a headache and fatigue were observed. No significant elevation of alanine transaminase and aspartate aminotransferase activity, or bilirubin level were detected. Conclusions. Daclatasvir combination to asunaprevir or sofosbuvir demonstrated high efficacy, including that at treatment of patients with poor prognostic signs

A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel.

Decisions on public health issues are dependent on reliable epidemiological data. A comprehensive review of the literature was used to gather country-specific data on risk factors, prevalence, number of diagnosed individuals and genotype distribution of the hepatitis C virus (HCV) infection in selected European countries, Canada and Israel

Efficacy and safety of the Russian protease inhibitor narlaprevir at treatment-naive and earlier treated noncirrhotic patients with the 1st genotype chronic hepatitis C (PIONEER study)

Aim of investigation. To estimate efficacy and safety of narlaprevir (NVR) with ritonavir (RTV), pegilated interferon (peg-IFN) and ribavirin (RBV) at treatmentnaïve and earlier treated noncirrhotic patients with chronic hepatitis C caused by the 1st virus genotype in double blind placebo-controlled 3rd phase study (PIONEER). Material and methods. The main group received NVR (200 mg od orally) in combination to RTV (100 mg) and pegIFN/RBV for 12 weeks that was followed by peg-IFN/ RBV for 12 weeks. Comparison group received pegIFN/ RBV for 48 weeks, for the first 12 weeks in combination to placebo. Results. The sustained virologic response in 24 weeks after treatment termination (SVR24) in the main group (NVR/RTV, PEG IFN/RBV)) was achieved in 89.1% (163/183) of treatment-naïve and 69.7% (69/99) of earlier treated patients. SVR24 was achieved in 86.5% (32/37) of patients with relapse after previous peg-IFN/ RBV treatment course. The viral load decreased for the mean of 5.3 log10 in 2 weeks and 5.9 log10 in 4 weeks of treatment in the main group vs 1.5 log10 in 2 weeks and 2.5 log10 in 4 weeks in comparison group. In treatment-naïve patients from the main group SVR24 was achieved in 90.8% at initial METAVIR F0-F2 liver fibrosis stage and in 75% at F3 liver fibrosis stage. In those who were previously treated by peg-IFN/RBV, in the main group SVR-24 was attained in 72.6% at liver fibrosis stage F0-F2 and in 53.3% with F3 liver fibrosis stage. NVR/RTV addition to peg-IFN/RBV treatment did not alter safety profile as compared to peg-IFN/RBV therapy. Conclusions. In PIONEER study the narlaprevir combination therapy was characterized by high efficacy, convenience of administration and favorable safety profile

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieve

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become availabl