Quality of life and health utility index in type 2 diabetes mellitus patients with various forms of hypoglycemia receiving basal-bolus insulin therapy

Analysis of the results of observational program «Quality of life, symptoms of hypoglycemia and treatment satisfaction in patients with type 2 diabetes receiving basal-bolus insulin therapy» are presented. One thousand patients with type 2 diabetes mellitus (DM2) from ten regions of Russia were included in the above program. The quality of life of DM2 patients with different forms of hypoglycemia on insulin therapy and their distribution according to the grades of quality of life impairment were studied; the health utility index ( Ut) for various forms of hypoglycemia was determined. Quality of life in DM2 patients with hypoglycemia was lower than in those without hypoglycemia. Patients with severe and nocturnal hypoglycemia episodes recorded the expressed disturbances in quality of life; the majority of patients in this group had critical or severe quality of life impairment. On the basis of real-world practice data, the values of health utility index for patients with and without hypoglycemia were determined. The obtained values of health utility index can be used to calculate QALY in pharmacoeconomic analysis

Pharmacoeconomic analysis of use the oral hypoglycemic agents in patients with type 2 diabetes mellitus according to a real clinical practice

We aimed to conduct cost-utility analysis of two different regimens of the oral hypoglycemic therapy in 2 type diabetes mellitus (DM2). Methods. In the whole, 229 patients with DM2, receiving vildagliptin add-on to metformin (group 1) or sulphonylureas add-on to metformin (group 2) were enrolled in the study. Cost-utility ratio (CUR) was identified as a ratio of difference in total costs of treatment in the groups and difference in QALY in corresponding groups. The overall costs included direct costs of treatment as well as costs for treating of DM2 complications (severe hypoglycemia) and the costs related to the loss of GDP due to severe hypoglycemia events. Health utility value was evaluated for each patient on the basis of SF-6D questionnaire. Pharmacoeconomic expediency of treatment regimen was estimated by means of comparing the CUR and wiliness-to-pay ratio (WTP) for Russian Federation (RF). Results. The health utility value was higher in group 1 as compared to group 2: 0,757 vs 0,70 (p>0,05). The overall costs for treating one patient in group 1 during a year were 28 637,34 rubles, in group 2 - 10 231,55 rubles. CUR amounted 328 674,82 rubles and it was 4.4 times lower than upper border of WTP ratio in RF (1 457 400 rub.). Conclusion. The innovation treatment regimen with vildagliptin add-on to metformin is beneficial and may be considered as economically reasonable alternative to traditional treatment regimen with sulphonylureas add-on to metformin for DM2 patients in RF

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone

ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ НОВОГО СОРТА САФЛОРА КРАСИЛЬНОГО КРАСА СТУПИНСКАЯ

The data on new variety of false saffron Krasa Stupinskaya are presented. The false saffron is the break, phytosanitary, phytomeliorative, feeding, decorative, and oil crop. It is recommended to grow in all region of Russian Federation.Представлены данные о новом сорте сафлора красильного Краса Ступинская. Сафлор красильный является сидеральной, фитосанитарной, фитомелиоративной, кормовой, декоративной и перспективной масличной культурой. Рекомендуется для выращивания во всех регионах РФ

The Protein Partners of GTP Cyclohydrolase I in Rat Organs

GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat.A pulldown and proteomics approach were used to identify GCH1 interacting proteins in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein (GFRP) in rat liver by affinity purification followed by proteomics and validated six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1 interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself locates in mitochondria.GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1. Our finding indicates GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis

Тяжесть поражения коронарных артерий у больных ишемической болезнью сердца с различными вариантами гена рецептора витамина D и уровнем обеспеченности витамином D

Introduction. Vitamin D deficiency may be an independent predictor of coronary heart disease (CHD) and the severity of coronary atherosclerosis. The results of studies of the association of various polymorphisms of the vitamin D receptor (VDR) gene with the risk and severity of CHD are contradictory, which necessitates the study of genetic variants of the VDR gene and the characteristics of the clinical course of CHD in the Russian population.The objective was to determine the distribution of genotypes of TaqI, BsmI and ApaI of polymorphic variants of the VDR gene and the level of vitamin D sufficiency in CHD patients with varying severity of CHD, residents of St. Petersburg.Methods and materials. The study included 407 CHD patients and 318 patients without clinical signs of CHD of comparable age (p>0.05). All CHD patients underwent coronary angiography. Typing of the VDR gene variants was performed by polymerase chain reaction and subsequent restriction analysis. Determination of the level of 25(OH)D blood serum was carried out by enzyme immunoassay.Results. Vitamin D deficiency was detected in 82 % of CHD patients, the content of 25(OH)D in blood serum was lower in CHD patients who had 2 or more myocardial infarctions (MI) than in those who had one MI (p=0.03). Vitamin D deficiency is associated with a 3.6-fold increased risk of multivessel disease (p=0.01). The presence of the aa genotype and the a allele (ApaI), the bb genotype and the b allele of the VDR gene (BsmI) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries.Conclusion. Vitamin D deficiency is typical for CHD patients and is associated with the severity of coronary atherosclerosis. The presence of aa genotype and a allele (ApaI polymorphism), bb genotype and b allele of the VDR gene (BsmI polymorphism) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries. TaqI polymorphism of the VDR gene is not associated with the risk of CHD.Актуальность. Дефицит витамина D может быть независимым предиктором ишемической болезни сердца (ИБС) и тяжести коронарного атеросклероза. Результаты исследований связи различных полиморфизмов гена рецептора витамина D (VDR) с риском и тяжестью ИБС противоречивы, что обуславливает необходимость изучения генетических вариантов гена VDR и особенностей клинического течения ИБС в российской популяции.Введение. Дефицит витамина D может быть независимым предиктором ишемической болезни сердца (ИБС) и тяжести коронарного атеросклероза. Результаты исследований связи различных полиморфизмов гена рецептора витамина D (VDR) с риском и тяжестью ИБС противоречивы, что обуславливает необходимость изучения генетических вариантов гена VDR и особенностей клинического течения ИБС в российской популяции.Цель – определить распределения генотипов TaqI, BsmI и ApaI полиморфных вариантов гена рецептора витамина D и уровня обеспеченности витамином D у больных ИБС с различной тяжестью поражения коронарных артерий, жителей Санкт-Петербурга.Методы и материалы. В исследование включены 407 больных ИБС и 318 обследованных без клинических признаков ИБС, сопоставимого возраста (р>0,05). Всем больным ИБС была выполнена коронарография. Типирование вариантов гена VDR проводили методом полимеразной цепной реакции и последующего рестрикционного анализа. Определение уровня 25(OH)D сыворотки крови проводили иммуноферментным методом.Результаты. У 82 % больных ИБС выявлен дефицит витамина D, содержание 25(ОН)D сыворотки крови было ниже у больных ИБС, перенесших два и более инфаркта миокарда (ИМ), чем у перенесших один ИМ (р=0,03). Дефицит витамина D ассоциируется с повышением риска многососудистого поражения в 3,6 раза (р=0,01). Наличие aa­генотипа и а-аллеля (АраI), bb-генотипa и b-аллеля гена VDR (BsmI) ассоциируется с повышением риска ИБС и с тяжестью атеросклеротического поражения коронарных артерий.Заключение. Дефицит витамина D характерен для больных ИБС и ассоциируется с тяжестью коронарного атеросклероза. Наличие aa-генотипа и а-аллеля (АраI-полиморфизм), bb-генотипa и b-аллеля гена VDR (BsmI-полиморфизм) ассоциируется с повышением риска ИБС и с тяжестью атеросклеротического поражения коронарных артерий. TaqI-полиморфизм гена VDR не ассоциирован с риском ИБС

POTENTIAL APPLICATION OF NEW VARIETY OF FALSE SAFFRON KRASA STUPINSKAYA

The data on new variety of false saffron Krasa Stupinskaya are presented. The false saffron is the break, phytosanitary, phytomeliorative, feeding, decorative, and oil crop. It is recommended to grow in all region of Russian Federation

Quality of life, symptom profile and clinical efficacy of second-line treatment with dasatinib in patients with imatinib-resistant or -intolerant chronic myeloid leukemia: results of 2-year follow-up

The article is focused on the results of the multicenter observational study “Quality of life and symptom profile in patients with chronic myeloid leukemia in chronic phase in long-term follow-up of second-line treatment” (2012–2015). Thirty imatinib-resistant or-intolerant patients with chronic myeloid leukemia in chronic phase were observed in the real-world clinical setting during 24 months after start of second-line treatment with dasatinib. Mean age – 48 years old (SD = 13.1); males / females – 14 / 16; one third of patients were with comorbidity, Charlson Index – 0–5 scores. All the patients received dasatinib in the dosage of 100 mg daily. Study time points – 12, 18 and 24 months after second-line treatment start. Treatment outcomes were analyzed in terms of clinical efficacy and safety as well as in terms of patient-reported outcomes, including quality of life and symptom profile assessment. For quality of life and symptom assessment the SF-36 and CSP-CML questionnaires were used, respectively. Statisticallly significant changes in quality of life and symptom severity were analyzed by generalized estimated equation (GEE). Complete hematological response was observed in 96.3 % patients, complete cytogenetic response – in 66.6 % patients, complete or major molecular response – in 60 % patients. The acceptable tolerability of dasatinib treatment was shown during long-term follow-up: hematological and non-hematological serious adverse events were rare and didn’t lead to treatment discontinuation. Significant improvement of physical functioning, role physical functioning, role emotional functioning, vitality and mental health as compared to base-line parameters was observed (p < 0.05). The severity of a number pronounced symptoms decreased and the proportion of patients with severe symptoms reduced (p = 0.01) after 24 months of second-line treatment start. Quality of life treatment response in terms of stabilization or improvement was registered in 83 % of patients. The data of this real-world study in CML patients are in line with the results of clinical studies in terms of dasatinib treatment efficacy and safety. In addition, they demonstrate the value of patient-reported outcomes to evaluate benefits and risks of long-term dasatinib treatment from patient perspective