Матеріали інформаційно-методичного забезпечення дисципліни «Правоохоронне право (Суд)»

Одержані знання дозволять студентам сформувати фаховий світогляд, пізнати органічні зв’язки даної навчальної дисципліни з іншими академічними курсами. Вибіркова дисципліна «Правоохоронне право (Суд)» межує з такими правовими дисциплінами, як ”Судові та правоохоронні органи України”, «Цивільне право», «Кримінальне право», «Цивільний процес», «Кримінальний процес», «Адміністративне судочинство», «Господарське право», «Господарський процес» та інші.Вибіркова дисципліна «Правоохоронне право (Суд)» займає особливе місце в навчальному плані і є невід’ємним фактором правової системи й основним недержавним інститутом захисту особистості, її прав і свобод. Зміст цієї навчальної дисципліни складається із знань, що регулюють діяльність суду – захисника у сфері судочинства, судового захисту прав та інтересів людей

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment

Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism A Randomized Clinical Trial

Importance Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. Objective To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. Design, Setting, and Participants A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. Interventions Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. Main Outcomes and Measures The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. Results The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was −10.5% (95% CI, −17.5% to −3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%). Conclusions and Relevance Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety

Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing

Background: With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these “off-the-shelf” therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation. Recently, we showed proof of concept that low energy electron irradiation (LEEI) is a new method for NK-92 inactivation. LEEI has several advantages over gamma irradiation, including a faster reaction time, a more reproducible dose rate and much less requirements on radiation shielding. Here, LEEI was further evaluated as a promising alternative to gamma irradiation yielding cells with highly maintained cytotoxic effector function. Methods: Effectiveness and efficiency of LEEI and gamma irradiation were analyzed using NK-92 and CD123-directed CAR-NK-92 cells. LEE-irradiated cells were extensively characterized and compared to gamma-irradiated cells via flow cytometry, cytotoxicity assays, and comet assays, amongst others. Results: Our results show that both irradiation methods caused a progressive decrease in cell viability and are, therefore, suitable for inhibition of cell proliferation. Notably, the NKmediated specific lysis of tumor cells was maintained at stable levels for three days postirradiation, with a trend towards higher activities after LEEI treatment as compared to gamma irradiation. Both gamma irradiation as well as LEEI led to substantial DNA damage and an accumulation of irradiated cells in the G2/M cell cycle phases. In addition, transcriptomic analysis of irradiated cells revealed approximately 12-fold more differentially expressed genes two hours after gamma irradiation, compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in surface expression of CD56, but no changes in the levels of the activating receptors NKp46, NKG2D, or NKp30. Conclusions: The presented data show that LEEI inactivates (CAR-)NK-92 cells as efficiently as gamma irradiation, but with less impact on the overall gene expression. Due to logistic advantages, LEEI might provide a superior alternative for the manufacture of (CAR-)NK-92 cells for clinical application

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Economic evaluation of cinacalcet in the United States: the EVOLVE trial

Background: Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies. Objectives: The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective. Methods: We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses. Results: The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and$79,562 per quality-adjusted life-year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of$115,876 per QALY. The model was most sensitive to the treatment effect on mortality. Conclusions: In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis

Biorthogonal spline-wavelets on the interval - stability and moment conditions

This paper is concerned with the construction of biorthogonal multiresolution analyses on [0, 1] such that the corresponding wavelets realize any desired order of moment conditions throughout the interval. Our starting point is the family of biorthogonal pairs consisting of cardinal B-splines and compactly supported dual generators on R developed by Cohen, Daubechies and Feauveau. In contrast to previous investigations we preserve the full degree of polynomial reproduction also for the dual multiresolution and prove in general that the corresponding modifications of dual generators near the end points of the interval still permit the biorthogonalization of the resulting bases. The subsequent construction of compactly supported biorthogonal wavelets is based on the concept of stable completions. As a first step we derive an initial decomposition of the spline spaces where the complement spaces between two successive levels are spanned by compactly supported splines which form uniformly stable bases on each level. As a second step these initial complements are then projected into the desired complements spanned by compactly supported biorthogonal wavelets. Since all generators and wavelets on the primal as well as on the dual side have finitely supported masks the corresponding decomposition and reconstruction algorithms are simple and efficient. The desired number of vanishing moments is implied by the polynomial exactness of the dual multiresolution. Again due to the polynomial exactness the primal and dual spaces satisfy corresponding Jackson estimates. In addition, Bernstein inequalities can be shown to hold for a range of Sobolev norms depending on the regularity of the primal and dual wavelets. Then it follows from general principles that the wavelets form Riesz bases for L_2 ([0, 1]) and that weighted sequence norms for the coefficients of such wavelet expansions characterize Sobolev spaces and their duals on [0, 1] within a range depending on the parameters in the Jackson and Bernstein estimates. (orig.)Available from TIB Hannover: RR 5549(265)+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis

Background: This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis. Methods: This study had double-blind and open-label phases. Eligible patients aged 6-<18years were randomized to cinacalcet (starting dose 0.20mg/kg) or placebo. The primary endpoint was 30% reduction from baseline in mean intact parathyroid hormone (iPTH). Secondary endpoints included mean iPTH 300pg/mL; percentage change from baseline in corrected total serum calcium, phosphorus, and calcium phosphorus product (CaxP); and safety. Results: The double-blind phase comprised 43 patients (cinacalcet, n=22; placebo, n=21). Nineteen months into the study, regulatory authorities were notified of a fatality; the study was subsequently terminated after a 14-month clinical hold. Before the hold, 12 patients (55%) on cinacalcet and four (19%) on placebo achieved the primary endpoint (p=0.017), and 27% and 24%, respectively, achieved iPTH 300pg/mL. The between-group differences (95% CI) in percentage changes for total serum calcium, phosphorus, and CaxP were -4% (-9 to 1%), -6% (-21 to 8%), and -10% (-23 to 3%). The mean maximum actual weight-adjusted daily cinacalcet dosage administered was 0.99mg/kg/day. Overall, 82% of patients on cinacalcet and 86% on placebo had 1 treatment-emergent adverse event; the most common were vomiting (32%, 24%, respectively), hypocalcemia (23%, 19%), nausea (18%, 14%), and hypertension (14%, 24%). Conclusions: Despite early termination, efficacy and safety outcomes observed with cinacalcet in children with SHPT on dialysis were consistent with adult observations, suggesting cinacalcet may meet an unmet medical need for this population