The Science of the total environment, Jan 15, 2018
Three peat cores were extracted from the Kovářská Bog in the central Ore Mountains to study anthr... more Three peat cores were extracted from the Kovářská Bog in the central Ore Mountains to study anthropogenic pollution generated by mining and metallurgy. The core profiles were C dated, and concentrations of selected elements were determined by ICP MS and HG-AAS. Principal component analysis indicated that Pb, Cu, As and Ag may be useful elements for the reconstruction of historical atmospheric pollution. Total and anthropogenic accumulation rates (ARs) of Pb, Cu and As estimated for the last ca. 3500years showed similar chronologies, and revealed twelve periods of elevated ARs of Pb, As and Cu related to possible mining and metallurgic activities. In total, four periods of elevated ARs of Pb, Cu and As were detected during the Middle and Late Bronze Ages, including a distinct Late Bronze Age pollution event between 1030BCE and 910BCE. The Iron Age included three episodes of increased ARs of Pb and As; the first and the most distinctive episode, recorded between 730 and 440BCE, was si...
Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthriti... more Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthritis (RA). The efficacy of treatment of rheumatoid arthritis with MTX is between 46 % and 65 % (as assessed by ACR 20). Pharmacogenetics deals with genetic predisposition of the patient to respond to the treatment. The aim of the study was to determine whether single nucleotide polymorphism (SNP) C677T (rs1801133) of the MTHFR gene are predictive of peroral MTX effi¬cacy or are associated with lower change of DAS28 (ΔDAS 28) after a 6-month MTX treatment in RA adult patient cohort of the East Bohemian populati¬on. The 120 patients were enrolled in the study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 RA criteria, and currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with DMARDs (n = 55). Genotyping was performed using qPCR allelic discri¬mination. We did not found any association of C677T SNP on MTX treatment i...
Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbid... more Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbidity or mortality of patients and add to the cost of the therapy. The second part of our long-term research project was carried out to identify the real condition of drug incompatibilities in critically ill patients in an intensive care unit (ICU) at department of gerontology and metabolism in university hospital. Materials & Methods: Prospective analysis of 50 patients with multi-organ failure, intoxications and serious infections admitted to the ICU between December 2010 and June 2011 with at least 2 different intravenous drugs were done. This analysis led to identify the frequency of incompatibilities between intravenous drugs. Based on previous retrospective acquired data, standard operating procedures (SOP) were made and the training of physicians is starting. Results: From 6224 drug pairs given to the 50 patients on ICU, 1,03% of drug pairs were incompatible. Into the most frequent ...
all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or ... more all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η 2 = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2013
Aim To explore the relationship between visuospatial memory, weak central coherence, and eating d... more Aim To explore the relationship between visuospatial memory, weak central coherence, and eating disorder (ED) symptoms in anorexia nervosa (AN) inpatients. Sample 31 female AN inpatients. Methods Rey complex figure test (RCFT) was used to assess both visuospatial memory and central coherence. RCFT consisted of copy and recall trials. ED symptoms were assessed by The Eating Disorder Examination-Questionnaire (EDE-Q) and The Clinical and Research Inventory for Eating Disorders (CR-EAT). Results We found a statistically significant negative correlation between recall accuracy and the total EDE-Q score. Furthermore, recall accuracy and recall central coherence significantly negatively correlate with several EDE-Q and CR-EAT scales. Conclusions These findings may contribute to a better understanding of cognitive impairments specifically in ED, and to refining interventions aiming at their improvement.
Objectives: EN-RAGE is extracellular newly identified receptor for advanced glycation end-product... more Objectives: EN-RAGE is extracellular newly identified receptor for advanced glycation end-products binding protein playing a role in inflammation. The aim was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis patients (HD). Design and methods: This is a prospective observational cohort study in 261 HD patients followed up for five years. Laboratory parameters were measured at the beginning of the study. Results: EN-RAGE was slightly but unsignificantly increased in HD patients compared with healthy controls and correlated significantly with inflammatory markers. Univariate Cox analysis demonstrated EN-RAGE as a significant predictor for mortality due to infection (HR (95%CI): 1.305 (1.063-1.602), per standard deviation, p = 0.01), but this significance disappeared in multivariate Cox analysis when CRP was included into the model. Conclusions: Our study demonstrates EN-RAGE as an inflammatory biomarker. It is related to mortality of HD patients due to infection, but in our study, it did not provide additional information to CRP.
Background: Malnutrition, inflammation, and oxidative stress are interrelated mechanisms linked t... more Background: Malnutrition, inflammation, and oxidative stress are interrelated mechanisms linked to the progression of cardiovascular disease and prognosis of long-term hemodialysis (HD) patients. In this study, we focus on antioxidant vitamins and trace elements and the relationship of their serum levels to the prognosis of long-term HD patients. Study Design: Prospective observational cohort study. Setting & Participants: 261 long-term HD patients prospectively followed up for 5 years (2003-2008). The control group consisted of 66 healthy participants. Predictors: Retinol, ␣-tocopherol, retinol-binding protein 4 (RBP-4), and the trace elements zinc and selenium. Outcomes: Mortality and cardiovascular mortality. During follow-up, 146 patients (56%) died, and for 71 of these, death was due to cardiovascular causes. Measurements: Retinol, ␣-tocopherol, RBP-4, zinc, selenium, and basic nutritional and inflammatory parameters measured at the beginning of the study. Results: Retinol and RBP-4 levels were significantly increased, whereas retinol:RBP-4 ratio and ␣-tocopherol, selenium, and zinc levels were decreased in HD patients compared with controls (retinol, 0.017 Ϯ 0.006 g/dL in HD patients vs 0.010 Ϯ 0.002 g/dL in controls; P Ͻ 0.001). Lower retinol level was found to be a significant independent predictor of overall and cardiovascular mortality in multivariate Cox analysis (HR, 0.733 [95% CI, 0.599-0.896], P ϭ 0.002, and 0.694 [95% CI, 0.511-0.942], P ϭ 0.02, per 1 SD, respectively). The worst prognoses for patients with lower retinol levels were observed when these were combined with low albumin levels. Limitations: Sample size, investigation of prevalent, not incident, dialysis patients. Conclusions: This is the first study showing a lower retinol level as an independent predictor of overall and cardiovascular mortality in HD patients. It has to be elucidated whether the beneficial effects of higher serum retinol levels should be attributed to only better nutritional support or also to retinol's role in immune response and differentiation.
Background Identifying genetic predictors of methotrexate (MTX) therapy response in patients with... more Background Identifying genetic predictors of methotrexate (MTX) therapy response in patients with rheumatoid arthritis (RA) may have importance for clinical benefit optimalization. MTX therapeutic effect is achieved by inhibiting enzymes of the folate and adenosine pathways. MTX response is mainly influenced by 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme activity. Objectives The aim of the study was to determine whether single nucleotide polymorphisms (SNPs) in the MTHFR gene are predictive of MTX response according to the change of DAS28 after a 6-month MTX treatment in RA patient cohort of the East Bohemian population. The two SNPs 677C>T (rs1801133) and 1298A>C (rs1801131) of the MTHFR gene have been genotyped. Methods Monocentric, regional, retrospective and prospective, cross-sectional study. The 118 patients (mean age 57 years, SD ±12.7, age of 27- 83 years, and 31 male – 26%) were enrolled in study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 criteria, and currently or previously taking MTX oral treatment, either as monotherapy (n=16) or in combination with DMRDs or corticoids (n=102). The concomitant treatment were sulfasalazin (n=18), leflunomide (n=10), hydrochloroquin (n=18), cyclosporine (n=8), biologics (n=7) and glucocorticoids (n=86). Treatment outcome was evaluated using DAS28 score and based on EULAR criteria at the beginning of MTX treatment, prospectively at entry into study or retrospectively from patients' file (in case of patients with history of MTX treatment) and after a 6-month therapy. Genotyping assays: Leukocyte genomic DNA will be extracted from whole blood using a QIAamp DNA Blood Mini Kit (Quiagen). Genotyping was performed by qPCR allelic discrimination using commercial TaqMan (allele-specific) assays (LifeTechnologies) or sequencing. Statistical analysis was carried out in PASW® 18 software. Statistical dependences were tested by GLM (Generalized Linear Models), with bootstrap procedure. Results Results of the study thus show that higher dose of MTX lead to better response of DAS28, i.e. 1.19 DAS28/10mg MTX (p=0.02). In case of polymorphism 677C>T, mean response on MTX treatment (expressed by decrease of DAS 28 after a 6-months treatment) in CC homozygotes was found 1.59 DAS/10mg MTX (median of MTX dose); CI 95% = (0.12, 3.06); p=0.034, in CT heterozygotes 0.70 DAS28/10mg; CI 95% = (-0.82, 2.22); p=0.36, and in homozygotes TT 1.83 DAS 28/10mg; CI 95% = (-1.70, 5.37); p=0.31. Regarding 1298A>C polymorphism, in AA homozygotes DAS 28 changed by 1.92 DAS28/10mg; CI 95% =(0.43, 3.41); p=0.012, in AC heterozygotes 0.43 DAS28/10mg; CI 95% = (-1.08, 1.94); p=0.57, and in CC homozygotes 1.33 DAS 28/10mg; CI 95% = (-1.59, 4.24); p=0.37. Conclusions Our data shows that significant response to MTX treatment was found only in case of 677CC and 1298AA homozygous patients. Significant decrease of DAS 28 was associated with MTX dose in 677CC and 1298AA homozygotes. These results indicate the association of MTHFR polymorphisms with MTX response. Acknowledgements Supported by MH CZ - DRO (UHHK, 00179906) Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4365
The standard SEIR equation-based models represent the state-of-the-art approach in epidemiologica... more The standard SEIR equation-based models represent the state-of-the-art approach in epidemiological modelling. Their drawbacks include unrealistic infectionrelated contact estimates and difficulties in modelling nonpharmaceutical interventions, such as contact reductions or partial closures. In this paper, we present our agent-based model that addresses the above-mentioned issues. It works with a population of individuals (agents) and their contacts are modelled as a multi-graph social network according to real data based on a Czech county. Custom algorithmic procedures simulating testing, quarantine and partial closures of various contact types are implemented. The model can serve as a tool for relative comparison of the efficacy of various policies. It was also used for a study comparing various interventions in Czech primary and secondary schools, using a graph based on real data from a selected Czech school.
Background Oral anticoagulants are established drugs of choice for the prevention and treatment o... more Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic. Setting Retrospective observational pharmacovigilance study. Methods Adverse drug reaction reports were obtained from the State Institute for Drug Control between January 2005 and November 2017. Reports related to warfarin, dabigatran, apixaban, and rivaroxaban received from healthcare professionals and patients were analyzed. Main outcome measure Frequency and nature of adverse drug reactions reported to oral anticoagulants. Results In total, 297 reports containing 672 adverse drug reactions were received; 269 reports were sent by healthcare professionals (85% by physicians). In 65% of all reports, reactions were due to direct oral anticoagulants. A higher total number of adverse ...
Rationale, aims, and objectives: Falls are among the major problems occurring in hospital setting... more Rationale, aims, and objectives: Falls are among the major problems occurring in hospital setting, when drugs are viewed as important modifiable risk factor of falling. The aim was to analyse the effect of pharmacotherapy on the risk of falls in hospitalized patients. Methods: A multicentre prospective case-control study was conducted in 2017 retrieving data from four hospitals in South Bohemia, Czech Republic. An online database was constructed to collect patient and fall-related data. Each fall that occurred during hospitalization was assigned to appropriate controls (no fall during hospitalization) based on gender, age, length of hospitalization, and the number of drugs. Univariate and multivariate correlations were performed with a significance level of P < .05. Results: A total of 222 fall cases (107 males; median age, 81 y) and 1076 controls (516 males; median age, 80 y) were included. According to the first ATC level classification, drugs from groups S, N, and P were significantly associated with fall-related risk compared with controls (P < .05); further analysis of ATC levels showed that only psycholeptics (N05), antipsychotics (N05A), and tiapride were significantly associated with falls. Regression analysis revealed use of psycholeptics N05 (OR = 2.06; 95% CI, 1.56-2.76), or ophthalmologicals S01 (OR = 2.72; 95% CI, 1.37-5.41), as factors with the highest fall-related risk. Conclusions: Apart from the commonly considered fall-risk increasing drugs, other groups, such as ophthalmologicals, should also be considered; however, regarding clinical practice, it is difficult to evaluate the effects of individual drugs in the context of other risk factors of falls, due to the multifactorial nature of falls.
Direct oral anticoagulants (DOACs) have gradually entered the Czech market as alternatives to vit... more Direct oral anticoagulants (DOACs) have gradually entered the Czech market as alternatives to vitamin K antagonists and parenteral anticoagulants since 2008. Considering the eventual changes, the aim was to evaluate drug use and expenditure patterns on anticoagulants in the Czech Republic. A retrospective utilization study was conducted retrieving data from the State Institute for Drug Control database, including reports on drug supplies from distributors with anatomical therapeutic chemical classification (ATC) codes B01AA, B01AB, B01AE, B01AF, and B01AX. The utilization on national level was expressed as the ratio of the number of defined daily doses per 1000 inhabitants per day (DDD/TID). Expenditures on all anticoagulants were also assessed. Data was analyzed using PASW (version 18.0). Between January 2007 and December 2017, the national anticoagulant utilization rate increased continuously from 14.15 to 27.67 DDD/TID. The use of DOACs was 0.002 DDD/TID in 2008, increased to 6.04 DDD/TID in 2017. Warfarin utilization, after a small decrease in 2008, has shown nearly stable levels in the recent years (70.9% of all anticoagulants; mean 11.55 DDD/TID over the last 5 years), while its increase was halted by the spread of DOACs utilization (p < 0.05). In 2017, over half of the expenditures (51.1%) were due to oral anticoagulants, whereof 47.6% was related to DOACs. The results reflected a growing utilization and increasing costs of all anticoagulants, especially in DOACs at the expense of warfarin. Still, additional information regarding patient persistence and prescribing patterns is needed for a better understanding of oral anticoagulant utilization. Keywords Anticoagulants • Drug utilization • Warfarin • DOAC • Czech Republic Highlights • Generally, little evidence about anticoagulant utilization has been published so far, especially in Central Europe. • Total use of both oral and parenteral anticoagulants has been continuously increasing in the last decade. • Growing utilization and increasing costs was especially in a group of DOACs. • Despite the slight decrease of warfarin utilization after the approval of dabigatran, its utilization has shown a nearly stable level in the recent years. • Increasing DOACs utilization should be perceived in terms of proper use and management.
Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Mo... more Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).
chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly... more chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly used in the treatment of sHPT in patients with CKD. The purpose of this prospective clinical study was to assess the influence of treatment with cinacalcet on the markers of both oxidative stress and total antioxidant capacity in hemodialysed patients with sHPT. METHODS: In 58 patients treated with hemodialysis 3 times per week and with persistent serum PTH concentration above 300 pg/ml plasma Advanced Oxygenation Protein Products (AOPP), total antioxidant capacity-ImAnOx (TAS/TAC), serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 6 months of treatment. A log transformation was used to normalize the distribution of PTH, AOPP and ImAnOx concentrations, thus these results are presented as geometric means with 95% CI. Paired t-test was then used to assess the variables changes over time. Correlation coefficients were calculated using Spearman's rank correlation. RESULTS: Serum PTH concentration decreased significantly from 895 (748-1070) pg/ ml to 384 (289-510) pg/ml after 6 month of treatment; p<0.0001. Mean serum calcium and phosphate concentrations remained stable. Plasma AOPP concentration decreased significantly from 152 (126-185) mmol/l to 49 (43-57) mmol/l after 6 months of treatment; p<0.0001. Plasma antioxidant capacity (ImAnOx) significantly increased from 260 (251-270) mmol/l to 272 (264-280) mmol/l; p=0.047. After 6 months of treatment a significant, positive correlation was found between ImAnOx and the daily dose of cinacalcet (r=0,30; p=0.02). Also the change of plasma ImAnOx during treatment with cinacalcet significantly correlated with the daily dose of cinacalcet r=0.35; p=0.01. No significant correlations were found between plasma AOPP concentration or ImAnOx and PTH, nor their changes in time, respectively. CONCLUSIONS: 1. Six-month treatment with cinacalcet reduces oxidative stress in maintenance hemodialysis patients with sHPT. 2. This beneficial effect seems to be related rather to the direct action of cinacalcet than to the serum PTH concentration decrease.
Preparative Biochemistry & Biotechnology, 2017
Introduction: Isolation of genomic DNA is a key step in genetic analysis. The aim of the study wa... more Introduction: Isolation of genomic DNA is a key step in genetic analysis. The aim of the study was to evaluate the suitability of isolation of DNA from peripheral blood with manual salting out procedure and automated MagNA system under specific conditions. Experimental: The impact of storage conditions, type of material (whole blood or blood cells) and method used for DNA extraction were evaluated in terms of DNA yield, its purity and integrity. Fresh material, material stored at 2-8°C for 1-4 weeks and frozen at-80°C were tested. Results and Discussion: For fresh samples, salting out method gives higher yield than MagNA, irrespectively on material used. Neither the yield of salting out method nor its purity decreases during the storage of the samples in the fridge (2-8°C) during 4 weeks. Concerning MagNA, storage of blood cells in the fridge decreases the yield of DNA as
The intersection dimension of a graph G with respect to a class A of graphs is the minimum k such... more The intersection dimension of a graph G with respect to a class A of graphs is the minimum k such that G is the intersection of some k graphs on the vertex set V (G) belonging to A. In this paper we follow [ Kratochvíl J., Tuza Z.: Intersection dimensions of graph classes, Graphs and Combinatorics 10 (1994), 159-168 ] and show that for some pairs of graph classes A, B the intersection dimension of graphs from B with respect to A is unbounded.
Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbid... more Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbidity or mortality of patients and add to the cost of the therapy. This first part of the research project was the aim to identify the most frequent and relevant drug incompatibilities in critically ill patients. Methods: Retrospective analysis of 221 patients with multi-organ failure, intoxications and serious infections admitted to the ICU between January and June 2009 with at least 2 different intravenous drugs were done and the most frequent brands of intravenous medications used in the intensive care unit of gerontology and metabolism department in a teaching hospital were identified. Based on the data, standard operating procedures (SOP) were made and the training of physicians started. Results: From 14074 drug pairs potentially given to the patients on ICU through one i.v. line, 2.62% of drug pairs were incompatible. Into the most frequent incompatible drugs pertains ciprofloxacin, ...
Background: Some single nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX)... more Background: Some single nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). Objectives: The aim of this study was to determine whether SNPs in key MTX pathway genes might be predictive of an adverse drug reactions (ADR) and MTX discontinuation in RA patients treated with peroral MTX. Methods: There were 185 patients enrolled in the retrospective study, all of whom fulfilled the 1987 RA criteria of the American College of Rheumatology. The patients were currently or previously treated with peroral MTX. Genotyping was performed by quantitative PCR with allelic discrimination using commercial TaqMan (allele
The Science of the total environment, Jan 15, 2018
Three peat cores were extracted from the Kovářská Bog in the central Ore Mountains to study anthr... more Three peat cores were extracted from the Kovářská Bog in the central Ore Mountains to study anthropogenic pollution generated by mining and metallurgy. The core profiles were C dated, and concentrations of selected elements were determined by ICP MS and HG-AAS. Principal component analysis indicated that Pb, Cu, As and Ag may be useful elements for the reconstruction of historical atmospheric pollution. Total and anthropogenic accumulation rates (ARs) of Pb, Cu and As estimated for the last ca. 3500years showed similar chronologies, and revealed twelve periods of elevated ARs of Pb, As and Cu related to possible mining and metallurgic activities. In total, four periods of elevated ARs of Pb, Cu and As were detected during the Middle and Late Bronze Ages, including a distinct Late Bronze Age pollution event between 1030BCE and 910BCE. The Iron Age included three episodes of increased ARs of Pb and As; the first and the most distinctive episode, recorded between 730 and 440BCE, was si...
Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthriti... more Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthritis (RA). The efficacy of treatment of rheumatoid arthritis with MTX is between 46 % and 65 % (as assessed by ACR 20). Pharmacogenetics deals with genetic predisposition of the patient to respond to the treatment. The aim of the study was to determine whether single nucleotide polymorphism (SNP) C677T (rs1801133) of the MTHFR gene are predictive of peroral MTX effi¬cacy or are associated with lower change of DAS28 (ΔDAS 28) after a 6-month MTX treatment in RA adult patient cohort of the East Bohemian populati¬on. The 120 patients were enrolled in the study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 RA criteria, and currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with DMARDs (n = 55). Genotyping was performed using qPCR allelic discri¬mination. We did not found any association of C677T SNP on MTX treatment i...
Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbid... more Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbidity or mortality of patients and add to the cost of the therapy. The second part of our long-term research project was carried out to identify the real condition of drug incompatibilities in critically ill patients in an intensive care unit (ICU) at department of gerontology and metabolism in university hospital. Materials & Methods: Prospective analysis of 50 patients with multi-organ failure, intoxications and serious infections admitted to the ICU between December 2010 and June 2011 with at least 2 different intravenous drugs were done. This analysis led to identify the frequency of incompatibilities between intravenous drugs. Based on previous retrospective acquired data, standard operating procedures (SOP) were made and the training of physicians is starting. Results: From 6224 drug pairs given to the 50 patients on ICU, 1,03% of drug pairs were incompatible. Into the most frequent ...
all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or ... more all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η 2 = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2013
Aim To explore the relationship between visuospatial memory, weak central coherence, and eating d... more Aim To explore the relationship between visuospatial memory, weak central coherence, and eating disorder (ED) symptoms in anorexia nervosa (AN) inpatients. Sample 31 female AN inpatients. Methods Rey complex figure test (RCFT) was used to assess both visuospatial memory and central coherence. RCFT consisted of copy and recall trials. ED symptoms were assessed by The Eating Disorder Examination-Questionnaire (EDE-Q) and The Clinical and Research Inventory for Eating Disorders (CR-EAT). Results We found a statistically significant negative correlation between recall accuracy and the total EDE-Q score. Furthermore, recall accuracy and recall central coherence significantly negatively correlate with several EDE-Q and CR-EAT scales. Conclusions These findings may contribute to a better understanding of cognitive impairments specifically in ED, and to refining interventions aiming at their improvement.
Objectives: EN-RAGE is extracellular newly identified receptor for advanced glycation end-product... more Objectives: EN-RAGE is extracellular newly identified receptor for advanced glycation end-products binding protein playing a role in inflammation. The aim was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis patients (HD). Design and methods: This is a prospective observational cohort study in 261 HD patients followed up for five years. Laboratory parameters were measured at the beginning of the study. Results: EN-RAGE was slightly but unsignificantly increased in HD patients compared with healthy controls and correlated significantly with inflammatory markers. Univariate Cox analysis demonstrated EN-RAGE as a significant predictor for mortality due to infection (HR (95%CI): 1.305 (1.063-1.602), per standard deviation, p = 0.01), but this significance disappeared in multivariate Cox analysis when CRP was included into the model. Conclusions: Our study demonstrates EN-RAGE as an inflammatory biomarker. It is related to mortality of HD patients due to infection, but in our study, it did not provide additional information to CRP.
Background: Malnutrition, inflammation, and oxidative stress are interrelated mechanisms linked t... more Background: Malnutrition, inflammation, and oxidative stress are interrelated mechanisms linked to the progression of cardiovascular disease and prognosis of long-term hemodialysis (HD) patients. In this study, we focus on antioxidant vitamins and trace elements and the relationship of their serum levels to the prognosis of long-term HD patients. Study Design: Prospective observational cohort study. Setting & Participants: 261 long-term HD patients prospectively followed up for 5 years (2003-2008). The control group consisted of 66 healthy participants. Predictors: Retinol, ␣-tocopherol, retinol-binding protein 4 (RBP-4), and the trace elements zinc and selenium. Outcomes: Mortality and cardiovascular mortality. During follow-up, 146 patients (56%) died, and for 71 of these, death was due to cardiovascular causes. Measurements: Retinol, ␣-tocopherol, RBP-4, zinc, selenium, and basic nutritional and inflammatory parameters measured at the beginning of the study. Results: Retinol and RBP-4 levels were significantly increased, whereas retinol:RBP-4 ratio and ␣-tocopherol, selenium, and zinc levels were decreased in HD patients compared with controls (retinol, 0.017 Ϯ 0.006 g/dL in HD patients vs 0.010 Ϯ 0.002 g/dL in controls; P Ͻ 0.001). Lower retinol level was found to be a significant independent predictor of overall and cardiovascular mortality in multivariate Cox analysis (HR, 0.733 [95% CI, 0.599-0.896], P ϭ 0.002, and 0.694 [95% CI, 0.511-0.942], P ϭ 0.02, per 1 SD, respectively). The worst prognoses for patients with lower retinol levels were observed when these were combined with low albumin levels. Limitations: Sample size, investigation of prevalent, not incident, dialysis patients. Conclusions: This is the first study showing a lower retinol level as an independent predictor of overall and cardiovascular mortality in HD patients. It has to be elucidated whether the beneficial effects of higher serum retinol levels should be attributed to only better nutritional support or also to retinol's role in immune response and differentiation.
Background Identifying genetic predictors of methotrexate (MTX) therapy response in patients with... more Background Identifying genetic predictors of methotrexate (MTX) therapy response in patients with rheumatoid arthritis (RA) may have importance for clinical benefit optimalization. MTX therapeutic effect is achieved by inhibiting enzymes of the folate and adenosine pathways. MTX response is mainly influenced by 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme activity. Objectives The aim of the study was to determine whether single nucleotide polymorphisms (SNPs) in the MTHFR gene are predictive of MTX response according to the change of DAS28 after a 6-month MTX treatment in RA patient cohort of the East Bohemian population. The two SNPs 677C>T (rs1801133) and 1298A>C (rs1801131) of the MTHFR gene have been genotyped. Methods Monocentric, regional, retrospective and prospective, cross-sectional study. The 118 patients (mean age 57 years, SD ±12.7, age of 27- 83 years, and 31 male – 26%) were enrolled in study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 criteria, and currently or previously taking MTX oral treatment, either as monotherapy (n=16) or in combination with DMRDs or corticoids (n=102). The concomitant treatment were sulfasalazin (n=18), leflunomide (n=10), hydrochloroquin (n=18), cyclosporine (n=8), biologics (n=7) and glucocorticoids (n=86). Treatment outcome was evaluated using DAS28 score and based on EULAR criteria at the beginning of MTX treatment, prospectively at entry into study or retrospectively from patients' file (in case of patients with history of MTX treatment) and after a 6-month therapy. Genotyping assays: Leukocyte genomic DNA will be extracted from whole blood using a QIAamp DNA Blood Mini Kit (Quiagen). Genotyping was performed by qPCR allelic discrimination using commercial TaqMan (allele-specific) assays (LifeTechnologies) or sequencing. Statistical analysis was carried out in PASW® 18 software. Statistical dependences were tested by GLM (Generalized Linear Models), with bootstrap procedure. Results Results of the study thus show that higher dose of MTX lead to better response of DAS28, i.e. 1.19 DAS28/10mg MTX (p=0.02). In case of polymorphism 677C>T, mean response on MTX treatment (expressed by decrease of DAS 28 after a 6-months treatment) in CC homozygotes was found 1.59 DAS/10mg MTX (median of MTX dose); CI 95% = (0.12, 3.06); p=0.034, in CT heterozygotes 0.70 DAS28/10mg; CI 95% = (-0.82, 2.22); p=0.36, and in homozygotes TT 1.83 DAS 28/10mg; CI 95% = (-1.70, 5.37); p=0.31. Regarding 1298A>C polymorphism, in AA homozygotes DAS 28 changed by 1.92 DAS28/10mg; CI 95% =(0.43, 3.41); p=0.012, in AC heterozygotes 0.43 DAS28/10mg; CI 95% = (-1.08, 1.94); p=0.57, and in CC homozygotes 1.33 DAS 28/10mg; CI 95% = (-1.59, 4.24); p=0.37. Conclusions Our data shows that significant response to MTX treatment was found only in case of 677CC and 1298AA homozygous patients. Significant decrease of DAS 28 was associated with MTX dose in 677CC and 1298AA homozygotes. These results indicate the association of MTHFR polymorphisms with MTX response. Acknowledgements Supported by MH CZ - DRO (UHHK, 00179906) Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4365
The standard SEIR equation-based models represent the state-of-the-art approach in epidemiologica... more The standard SEIR equation-based models represent the state-of-the-art approach in epidemiological modelling. Their drawbacks include unrealistic infectionrelated contact estimates and difficulties in modelling nonpharmaceutical interventions, such as contact reductions or partial closures. In this paper, we present our agent-based model that addresses the above-mentioned issues. It works with a population of individuals (agents) and their contacts are modelled as a multi-graph social network according to real data based on a Czech county. Custom algorithmic procedures simulating testing, quarantine and partial closures of various contact types are implemented. The model can serve as a tool for relative comparison of the efficacy of various policies. It was also used for a study comparing various interventions in Czech primary and secondary schools, using a graph based on real data from a selected Czech school.
Background Oral anticoagulants are established drugs of choice for the prevention and treatment o... more Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic. Setting Retrospective observational pharmacovigilance study. Methods Adverse drug reaction reports were obtained from the State Institute for Drug Control between January 2005 and November 2017. Reports related to warfarin, dabigatran, apixaban, and rivaroxaban received from healthcare professionals and patients were analyzed. Main outcome measure Frequency and nature of adverse drug reactions reported to oral anticoagulants. Results In total, 297 reports containing 672 adverse drug reactions were received; 269 reports were sent by healthcare professionals (85% by physicians). In 65% of all reports, reactions were due to direct oral anticoagulants. A higher total number of adverse ...
Rationale, aims, and objectives: Falls are among the major problems occurring in hospital setting... more Rationale, aims, and objectives: Falls are among the major problems occurring in hospital setting, when drugs are viewed as important modifiable risk factor of falling. The aim was to analyse the effect of pharmacotherapy on the risk of falls in hospitalized patients. Methods: A multicentre prospective case-control study was conducted in 2017 retrieving data from four hospitals in South Bohemia, Czech Republic. An online database was constructed to collect patient and fall-related data. Each fall that occurred during hospitalization was assigned to appropriate controls (no fall during hospitalization) based on gender, age, length of hospitalization, and the number of drugs. Univariate and multivariate correlations were performed with a significance level of P < .05. Results: A total of 222 fall cases (107 males; median age, 81 y) and 1076 controls (516 males; median age, 80 y) were included. According to the first ATC level classification, drugs from groups S, N, and P were significantly associated with fall-related risk compared with controls (P < .05); further analysis of ATC levels showed that only psycholeptics (N05), antipsychotics (N05A), and tiapride were significantly associated with falls. Regression analysis revealed use of psycholeptics N05 (OR = 2.06; 95% CI, 1.56-2.76), or ophthalmologicals S01 (OR = 2.72; 95% CI, 1.37-5.41), as factors with the highest fall-related risk. Conclusions: Apart from the commonly considered fall-risk increasing drugs, other groups, such as ophthalmologicals, should also be considered; however, regarding clinical practice, it is difficult to evaluate the effects of individual drugs in the context of other risk factors of falls, due to the multifactorial nature of falls.
Direct oral anticoagulants (DOACs) have gradually entered the Czech market as alternatives to vit... more Direct oral anticoagulants (DOACs) have gradually entered the Czech market as alternatives to vitamin K antagonists and parenteral anticoagulants since 2008. Considering the eventual changes, the aim was to evaluate drug use and expenditure patterns on anticoagulants in the Czech Republic. A retrospective utilization study was conducted retrieving data from the State Institute for Drug Control database, including reports on drug supplies from distributors with anatomical therapeutic chemical classification (ATC) codes B01AA, B01AB, B01AE, B01AF, and B01AX. The utilization on national level was expressed as the ratio of the number of defined daily doses per 1000 inhabitants per day (DDD/TID). Expenditures on all anticoagulants were also assessed. Data was analyzed using PASW (version 18.0). Between January 2007 and December 2017, the national anticoagulant utilization rate increased continuously from 14.15 to 27.67 DDD/TID. The use of DOACs was 0.002 DDD/TID in 2008, increased to 6.04 DDD/TID in 2017. Warfarin utilization, after a small decrease in 2008, has shown nearly stable levels in the recent years (70.9% of all anticoagulants; mean 11.55 DDD/TID over the last 5 years), while its increase was halted by the spread of DOACs utilization (p < 0.05). In 2017, over half of the expenditures (51.1%) were due to oral anticoagulants, whereof 47.6% was related to DOACs. The results reflected a growing utilization and increasing costs of all anticoagulants, especially in DOACs at the expense of warfarin. Still, additional information regarding patient persistence and prescribing patterns is needed for a better understanding of oral anticoagulant utilization. Keywords Anticoagulants • Drug utilization • Warfarin • DOAC • Czech Republic Highlights • Generally, little evidence about anticoagulant utilization has been published so far, especially in Central Europe. • Total use of both oral and parenteral anticoagulants has been continuously increasing in the last decade. • Growing utilization and increasing costs was especially in a group of DOACs. • Despite the slight decrease of warfarin utilization after the approval of dabigatran, its utilization has shown a nearly stable level in the recent years. • Increasing DOACs utilization should be perceived in terms of proper use and management.
Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Mo... more Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).
chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly... more chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly used in the treatment of sHPT in patients with CKD. The purpose of this prospective clinical study was to assess the influence of treatment with cinacalcet on the markers of both oxidative stress and total antioxidant capacity in hemodialysed patients with sHPT. METHODS: In 58 patients treated with hemodialysis 3 times per week and with persistent serum PTH concentration above 300 pg/ml plasma Advanced Oxygenation Protein Products (AOPP), total antioxidant capacity-ImAnOx (TAS/TAC), serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 6 months of treatment. A log transformation was used to normalize the distribution of PTH, AOPP and ImAnOx concentrations, thus these results are presented as geometric means with 95% CI. Paired t-test was then used to assess the variables changes over time. Correlation coefficients were calculated using Spearman's rank correlation. RESULTS: Serum PTH concentration decreased significantly from 895 (748-1070) pg/ ml to 384 (289-510) pg/ml after 6 month of treatment; p<0.0001. Mean serum calcium and phosphate concentrations remained stable. Plasma AOPP concentration decreased significantly from 152 (126-185) mmol/l to 49 (43-57) mmol/l after 6 months of treatment; p<0.0001. Plasma antioxidant capacity (ImAnOx) significantly increased from 260 (251-270) mmol/l to 272 (264-280) mmol/l; p=0.047. After 6 months of treatment a significant, positive correlation was found between ImAnOx and the daily dose of cinacalcet (r=0,30; p=0.02). Also the change of plasma ImAnOx during treatment with cinacalcet significantly correlated with the daily dose of cinacalcet r=0.35; p=0.01. No significant correlations were found between plasma AOPP concentration or ImAnOx and PTH, nor their changes in time, respectively. CONCLUSIONS: 1. Six-month treatment with cinacalcet reduces oxidative stress in maintenance hemodialysis patients with sHPT. 2. This beneficial effect seems to be related rather to the direct action of cinacalcet than to the serum PTH concentration decrease.
Preparative Biochemistry & Biotechnology, 2017
Introduction: Isolation of genomic DNA is a key step in genetic analysis. The aim of the study wa... more Introduction: Isolation of genomic DNA is a key step in genetic analysis. The aim of the study was to evaluate the suitability of isolation of DNA from peripheral blood with manual salting out procedure and automated MagNA system under specific conditions. Experimental: The impact of storage conditions, type of material (whole blood or blood cells) and method used for DNA extraction were evaluated in terms of DNA yield, its purity and integrity. Fresh material, material stored at 2-8°C for 1-4 weeks and frozen at-80°C were tested. Results and Discussion: For fresh samples, salting out method gives higher yield than MagNA, irrespectively on material used. Neither the yield of salting out method nor its purity decreases during the storage of the samples in the fridge (2-8°C) during 4 weeks. Concerning MagNA, storage of blood cells in the fridge decreases the yield of DNA as
The intersection dimension of a graph G with respect to a class A of graphs is the minimum k such... more The intersection dimension of a graph G with respect to a class A of graphs is the minimum k such that G is the intersection of some k graphs on the vertex set V (G) belonging to A. In this paper we follow [ Kratochvíl J., Tuza Z.: Intersection dimensions of graph classes, Graphs and Combinatorics 10 (1994), 159-168 ] and show that for some pairs of graph classes A, B the intersection dimension of graphs from B with respect to A is unbounded.
Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbid... more Introduction: Drug incompatibilities are relatively common in inpatients and may result in morbidity or mortality of patients and add to the cost of the therapy. This first part of the research project was the aim to identify the most frequent and relevant drug incompatibilities in critically ill patients. Methods: Retrospective analysis of 221 patients with multi-organ failure, intoxications and serious infections admitted to the ICU between January and June 2009 with at least 2 different intravenous drugs were done and the most frequent brands of intravenous medications used in the intensive care unit of gerontology and metabolism department in a teaching hospital were identified. Based on the data, standard operating procedures (SOP) were made and the training of physicians started. Results: From 14074 drug pairs potentially given to the patients on ICU through one i.v. line, 2.62% of drug pairs were incompatible. Into the most frequent incompatible drugs pertains ciprofloxacin, ...
Background: Some single nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX)... more Background: Some single nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). Objectives: The aim of this study was to determine whether SNPs in key MTX pathway genes might be predictive of an adverse drug reactions (ADR) and MTX discontinuation in RA patients treated with peroral MTX. Methods: There were 185 patients enrolled in the retrospective study, all of whom fulfilled the 1987 RA criteria of the American College of Rheumatology. The patients were currently or previously treated with peroral MTX. Genotyping was performed by quantitative PCR with allelic discrimination using commercial TaqMan (allele
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