Once versus three times daily dosing of oral budesonide for active Crohn's disease : A double-blind, double-dummy, randomised trial

Note: J.Pokrotnieks is in the list of the main authors of the article, as well as in the list of International Budenofalk Study Group collaboration list. His surname is made visible as the main author in this bibliographic record. Funding Information: The study was funded by Dr Falk Pharma GmbH, Freiburg, Germany . The study sponsor contributed to the design of the study in collaboration with the authors, funded the analysis of the data by an independent biostatistics company, worked in conjunction with the authors to interpret the data, and reviewed the draft manuscript. The sponsor was not involved in data collection. The final decision to publish was made by the first author (AD).Background: Oral budesonide 9. mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9. mg dose may improve adherence and thereby efficacy. Methods: An eight-week, double-blind, double-dummy randomised trial compared budesonide 9. mg OD versus 3. mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI < 150 at week 8 (last observation carried forward). Results: The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n = 377; 188 [9 mg OD], 189 [3 mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9. mg OD versus 3. mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of - 3.9% (95% CI [- 14.6%; 6.4%]; p = 0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3. mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥ 1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3 mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. Conclusions: Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3 mg TID dosing in mild-to-moderately active Crohn's disease.publishersversionPeer reviewe

Dependence of volume of blood perfusion in tissue of periodont from the degree of stress resistance and the anxiety level

To determine the dependence of the blood perfusion volume in the periodontal tissues on the degree of stress resistance and anxiety level in patients, we performed an examination, a survey and an index evaluation of periodontal disease. We also found out the level of emotional and psychological stress, the degree of anxiety and neurotic state in the subjects. Using laser Doppler flowmetry with a spectral analysis of blood flow oscillations, using the customary method on the LAKCOP apparatus, using a personalized kappa with a detachable fixative, the data on the parodontal blood supply parameters were determined. Patients with low stress tolerance and a high level of anxiety have significant differences from other study groups in virtually all parameters of dental status, in particular, with an increase in the level of psychoemotional tension, the intensity of carious diseases and inflammatory diseases of periodontal tissues increases. We got a significant decrease in the blood flow velocity in patients with psychoemotional stress .The rate of hemodynamics in the microcirculatory bed of periodontal tissues in patients of the control group is 1.5 times lower than in the patients of the third group and in 1.8 times in the patients of the fourth group.Для определения зависимости объёма перфузии крови в тканях пародонта от степени стрессоустойчивости и уровня тревожности у пациентов нами был проведен осмотр, опрос и индексная оценка пародонта. также мы выяснили уровень эмоционально-психологического напряжения, степень тревожности и невротического состояния у обследуемых. При помощи лазерной допплеровской флоуметрии со спектральным анализом колебаний кровотока по общепризнанной методике на аппарате ЛАККОП с применением персональной каппы со съемным фиксатором определили данные показателей кровоснабжения пародонта. Пациенты с низкой стрессоустойчивостью и высоким уровнем тревожности имеют достоверные отличия от других групп исследования фактически по всем параметрам стоматологического статуса, в частности, с увеличением уровня психоэмоционального напряжения возрастает интенсивность кариозных заболеваний и воспалительных заболеваний тканей пародонта. Получено значительное снижение скорости кровотока у пациентов в состоянии психоэмоционального напряжения. Скорость гемодинамики в микроциркуляторном русле тканей пародонта у пациентов контрольной группы в 1,5 раза ниже, чем у пациентов третьей группы и в 1,8 раза — у пациентов четвертой группы

The Analysis of Efficiency on the Base Discount System in the Pharmaceutical Organizations Depending on their Category and Level of the Competition on the Basis of Statistical Processing of Results Of Questionnaire

Authors set the task on the basis of questionnaire of pharmaceutical workers to analyse interrelation between efficiency use of discount system and such characteristics of the pharmaceutical organizations as category, location, competition level, and also lasting uses of discount system. Accurately expressed tendency of increase of conviction of staff of the pharmaceutical organizations in efficiency of use of discount programs at their long use is shown, interrelation of level of the competition in the developed pharmaceutical market, locations of the pharmaceutical organization and efficiency of use of discount systems. The used criteria of an assessment of efficiency of discount systems (increase in number of buyers, increase in the sum of the average check, etc.) by the pharmaceutical organizations depending on a site, competition level are considered

Studying the Factors Influencing a Choice of Devices for Carrying Out Inhalations on the Basis of Statistical Processing of Results Of Questionnaire

Authors set the object, to study the factors influencing a choice of buyers of devices for carrying out inhalation on the basis of statistical processing of results of questionnaire of buyers, to analyze interrelation between the factors influencing a choice and purchase of the device and gender and age characteristics of potential buyers. The role of the doctor, worker of a drugstore, the Internet sites in the course of a choice, opinion of consumers of different age categories on the most preferable sources of information on devices for carrying out inhalation is revealed, preferences of buyers at a choice of a place of commission of purchase of devices for carrying out inhalation are defined. Feature of respondents of sources of information and making decision on purchase, female and male concerning use is shown

Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy

Development of DNA Aptamers to Native EpCAM for Isolation of Lung Circulating Tumor Cells from Human Blood

We selected DNA aptamers to the epithelial cell adhesion molecule (EpCAM) expressed on primary lung cancer cells isolated from the tumors of patients with non-small cell lung cancer using competitive displacement of aptamers from EpCAM by a corresponding antibody. The resulting aptamers clones showed good nanomolar affinity to EpCAM-positive lung cancer cells. Confocal microscopy imaging and spectral profiling of lung cancer tissues confirmed the same protein target for the aptamers and anti-EpCAM antibodies. Furthermore, the resulted aptamers were successfully applied for isolation and detection of circulating tumor cells in clinical samples of peripheral blood of lung cancer patients

DNA Aptamers for the Characterization of Histological Structure of Lung Adenocarcinoma

Nucleic acid aptamers are becoming popular as molecular probes for identification and imaging pathology and, at the same time, as a convenient platform for targeted therapy. Recent studies have shown that aptamers may be effectively used for tumor characterization and as commercially available monoclonal antibodies. Here we present three DNA aptamers binding to whole transformed lung cancer tissues, including tumor cells, connective tissues, and blood vessels. Protein targets have been revealed using affinity purification followed by mass spectrometry analyses, and they have been validated using a panel of correspondent antibodies and 3D imaging of tumor tissues. Each of the proteins targeted by the aptamers is involved in cancer progression and most of them are crucial for lung adenocarcinoma. We propose the use of these aptamers in aptahistochemistry for the characterization of the histological structure of lung adenocarcinoma. The value of the presented aptamers is their application together or separately for indicating the spread of neoplastic transformation, for complex differential diagnostics, and for targeted therapy of the tumor itself as well as all transformed structures of the adjacent tissues. Moreover, it has been demonstrated that these aptamers could be used for intraoperative tumor visualization and margin assessment. Keywords: DNA-aptamer, lung adenocarcinoma, histological structur