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    Ales Kubena

    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... 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 arthritis (RA). The efficacy of treatment of rheumatoid arthritis with MTX is between 46 % and 65 % (as assessed by ACR 20). Pharmacogenetics deals... 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 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... 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 ...
    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... 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 epidemiological modelling. Their drawbacks include unrealistic infectionrelated contact estimates and difficulties in modelling nonpharmaceutical... 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 of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse... 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 ...
    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... 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).
    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... 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, ...
    Research Interests:
    To evaluate the efficiency of vitrectomy with peeling of the internal limiting membrane (ILM) in eyes with diffuse and/or cystoid nontractional diabetic macular edema (ME) refractory to macular laser photocoagulation. Histopathologic and... more
    To evaluate the efficiency of vitrectomy with peeling of the internal limiting membrane (ILM) in eyes with diffuse and/or cystoid nontractional diabetic macular edema (ME) refractory to macular laser photocoagulation. Histopathologic and morphometric analysis of the ILM in diabetic eyes was performed. Thickness of the ILM was correlated with the level of glykosylated hemoglobin (HbA1c) and other clinical factors. The prospective study involved 56 eyes of 52 diabetic patients with a mean age of 63 +/- 7.6 years. Vitrectomy with trypan blue-assisted ILM peeling was performed in standard way. Mean follow-up period was 8.7 months (range 3 - 19 months). The ILM was fixed immediately after peeling in 2.5% glutaraldehyde and submitted for electron microscopic evaluation. The ILM was photographed in standard magnification (x 5000) with the scale of 1 microm in the shot. Statistical analysis of the postoperative visual acuity (VA) in the study group of 56 eyes proved a general improvement wi...
    The study objective was to evaluate the impact of a restrictive antibiotic policy, efficacy of inpatient therapeutic and prophylactic antibiotic regimens and susceptibility patterns of infecting bacteria in 2000-2004. A 500-bed general... more
    The study objective was to evaluate the impact of a restrictive antibiotic policy, efficacy of inpatient therapeutic and prophylactic antibiotic regimens and susceptibility patterns of infecting bacteria in 2000-2004. A 500-bed general hospital in the Czech Republic. A retrospective computerized survey of antibiotic prescribing practices over a five-year period 2000-2004, using medical records and laboratory data from the hospital information system (HIS). Consumption of antibiotics expressed in defined daily doses (DDDs) and Euros per 1,000 bed days. Resistance to antibiotics, average length of hospital stay, rate of inpatients treated with antibiotics, number of nosocomial infections per 1,000 bed days, median length of hospital stay and total mortality. Due to a restrictive antibiotic policy implemented in 2002, the use of several antibiotics in 2003 was significantly reduced but the consumption of several other antibiotics rose in 2003. In comparison with 2001 the cost of antibiotic agents (in Euro per 1,000 inpatient days) fell significantly by 31% in 2003 Euro 969.07 vs. Euro 671.34). The hospital saved about Euro 29,288 after the first year of implementation of the new antibiotic policy. The use of restricted antibiotics increased by 8%; however, the expenditure decreased by 26%. For non-restricted antibiotics, the use and expenditure decreased by 71% and 41%, respectively. Consequently, a net reduction of 55% Euro 804.36 vs. Euro 359.36) was achieved. The intervention was effective in reducing the use and cost of antibiotics. The HIS is a helpful tool for observing and evaluating the impacts of the measures taken and can be used for assessment of pharmacotherapy outcomes.
    Background: Diabetic retinopathy (DR) is characterized by blood-retina barrier breakdown induced by local changes in the retina and systemic factors. We investigated vitreous and serum levels of glucose and uric acid (UA) in patients with... more
    Background: Diabetic retinopathy (DR) is characterized by blood-retina barrier breakdown induced by local changes in the retina and systemic factors. We investigated vitreous and serum levels of glucose and uric acid (UA) in patients with DR and aimed to describe their correlation with the grade of DR. Methods: Prospective study of 81 patients with DR and 48 non-diabetic controls. Biochemical analysis of vitreous and serum samples was performed. Results: UA and glucose concentrations in vitreous and serum were significantly higher in diabetic patients than in controls. Absolute ratios (vitreous level/serum level) of UA and glucose were higher in proliferative compared with non-proliferative DR. Conclusions: The results suggest that, apart from glucose, increased levels of UA in diabetic patients may also be involved in the pathogenesis and progression of DR.
    The plasma ADPN was 24.6 (13.9, 39.8) and 23.0 (13.9, 32.7)μg/ml for men and women, respectively (P=0.42). Multiple linear regression analysis showed that log-transformed ADPN was significantly negatively correlated with body fat mass... more
    The plasma ADPN was 24.6 (13.9, 39.8) and 23.0 (13.9, 32.7)μg/ml for men and women, respectively (P=0.42). Multiple linear regression analysis showed that log-transformed ADPN was significantly negatively correlated with body fat mass (P=0.008), residual glomerular filtration rate (P= ...
    The use of bisphosphonates (BPs) represents a standard therapy of bone metastatic disease from breast cancer and has been incorporated in many systemic international guidelines. We have tried to evaluate the use of BPs in current clinical... more
    The use of bisphosphonates (BPs) represents a standard therapy of bone metastatic disease from breast cancer and has been incorporated in many systemic international guidelines. We have tried to evaluate the use of BPs in current clinical practice across the Czech Republic. A covering letter, questionnaires and pre-paid envelopes were mailed to the head oncologists of 64 workplaces of Czech Oncology Society. Total 310 questionnaires were sent out. The questionnaire consisted of 23 questions. The questionnaires were completed and returned by 91 oncologists from 32 workplaces. Most of the responding oncologists worked at university hospitals (42%), the most frequent length of work experience was 5 to 10 years (30%) and the most frequent rate of breast cancer patients was from 10 to 25% (45%). Ninety-five percent of the oncologists regularly initiated BP therapy, and oral clodronate was the first choice BP (77%). Once initiated, the treatment was discontinued in less than 5% patients (24%). Seventy-one (79%) oncologists stated that the most important reason leading to therapy termination was impairment of performance status. The consensual agreement pointed out that it could be a fundamental step towards establishing the national treatment guidelines for the BP use in metastatic breast cancer patients.
    Lymnaeid snails of the genus Radix serve as intermediate hosts of some schistosomes and fasciolids. In Europe, delineation of species within the genus Radix is unresolved and, therefore, spectrum of snail hosts susceptible to trematode... more
    Lymnaeid snails of the genus Radix serve as intermediate hosts of some schistosomes and fasciolids. In Europe, delineation of species within the genus Radix is unresolved and, therefore, spectrum of snail hosts susceptible to trematode infections is under discussion. We used and compared three criteria for species delineation using snails collected at 43 localities. (a) Sequence analysis of ITS-2 rDNA disclosed that the collected snails belong to four species — R. auricularia (Linnaeus, 1758), R. peregra (Müller, 1774), R. lagotis (Schrank, 1803) and R. labiata (Rossmaessler, 1835) (criteria and names are based on the work of Bargues et al. 2001). Occurrence of R. peregra in the Czech Republic was confirmed by molecular data for the first time. (b) Characterization of reproductive system disclosed differences in location, size and shape of bursa copulatrix and its ductus. Unfortunately, some R. labiata specimens shared morphological features of reproductive organs with R. lagotis. (...
    This report presents a technical description of our agent-based epidemic model of a particular middle-sized municipality. We have developed a realistic model with 56 thousand inhabitants and 2.7 million of social contacts. These form a... more
    This report presents a technical description of our agent-based epidemic model of a particular middle-sized municipality. We have developed a realistic model with 56 thousand inhabitants and 2.7 million of social contacts. These form a multi-layer social network that serves as a base of our epidemic simulation. The disease is modeled by our extended SEIR model with parameters fitted to real epidemics data for Czech Republic. The model is able to simulate a whole range of non-pharmaceutical interventions on individual level, such as protective measures and physical distancing, testing, contact tracing, isolation and quarantine. The effect of government-issued measures such as contact restrictions in different environments (schools, restaurants, vendors, etc.) can also be simulated. The model is implemented in Python and is available as open source at: www.github.com/epicity-cz/model-m/releases
    Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as... more
    Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as infection and an unsatisfactory range of motion, which have influenced the survival of prostheses. Our retrospective study evaluated the data of hemophilic patients regarding changes in the development of the range of motion. The data and clinical outcomes of 72 total knee replacements in 45 patients with hemophilia types A and B were reviewed retrospectively. Patients were operated between 1998 and 2013. All of the patients were systematically followed up to record the range of motion and other parameters before and after surgery. The mean preoperative flexion contracture was 17° ± 11° (range, 0°-40°), and it was 7° ± 12° (range, 0°-60°) postoperatively. The mean flexion of the knee was 73° ± 30° (range, 5°-135°) before the operation and 80° ± 19°...
    Background: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2)... more
    Background: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. Methods: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. Results: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6-10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients...
    Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical... more
    Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical coherence tomography (OCT) and visual acuity (VA).Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR) and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT), cube volume (CV), cube average thickness (CAT), and serous retinal detachment (SRD).Results. In DME group, intravitreal concentrations of VEGF (p<0.001), UA (p=0.038), and total protein (p<0.001) were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (ƍ= 0.559,p=0.03) but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group...
    Drug incompatibilities are relatively common in inpatients and this may result in increased morbidity/mortality as well as add to costs. The aim of this 12 month study was to identify real incidences of drug incompatibilities in... more
    Drug incompatibilities are relatively common in inpatients and this may result in increased morbidity/mortality as well as add to costs. The aim of this 12 month study was to identify real incidences of drug incompatibilities in intravenous lines in critically ill patients in two intensive care units (ICUs). A prospective cross sectional study of 82 patients in 2 ICUs, one medical and one surgical in a 1500-bed university hospital. One monitor carried out observations during busy hours with frequent drug administration. Patients included in both ICUs were those receiving at least two different intravenous drugs. 6.82% and 2.16% of drug pairs were found to be incompatible in the two ICUs respectively. The study showed that a significant number of drug incompatibilities occur in both medical and surgical ICUs. It follows that the incidence of incompatibilities could be diminished by adhering to a few simple rules for medication administration, following by recommendations for multiple...
    Ischemic heart disease is the most frequent cause of both serious morbidity and mortality of adult population in developed countries. The main aim of the study was to carry out the analysis of general practitioners (GP) prescription of... more
    Ischemic heart disease is the most frequent cause of both serious morbidity and mortality of adult population in developed countries. The main aim of the study was to carry out the analysis of general practitioners (GP) prescription of evidence-based therapy in patients after myocardial infarction (MI). Data were retrospectively collected in 2011, by a single application with the help of software that GPs use in their surgeries. All patients of a particular GP who had MI in their history and who were at the time of data collection treated only by GPs (not by the specialists of internal medicine or cardiology) were always included. Four hundred ninety one patients were included in the study. The average age was 70.7 (+/- 11.6) and 69.2% of the involved patients were men. Seventy nine percent of patients used beta-blockers, 80% antiplatelet drugs, 77% statins and 79% used angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs). Forty four percent of pati...
    Generic substitution (GS) is an integral part of drug policy in many countries. Similarly to other countries its introduction in the Czech Republic gave rise to a vibrant discussion. The aim of the study was to map and analyze... more
    Generic substitution (GS) is an integral part of drug policy in many countries. Similarly to other countries its introduction in the Czech Republic gave rise to a vibrant discussion. The aim of the study was to map and analyze pharmacists' opinions of, attitudes towards and experiences with generic drugs and GS after the first year from its legislative embodiment in the Czech Republic. All 7,665 members of the Czech Chamber of Pharmacists were addressed to participate in a questionnaire survey between November 2008 and March 2009. The questionnaire consisted of 28 questions concerning the issue of generic drugs and GS and was divided into five sections. All collected data were analyzed using descriptive statistics and correlations were tested by selected parametric and non-parametric tests. A total of 615 completed questionnaire forms were returned (a questionnaire return rate of 8.0%). The demographic characteristics of the respondents were as follows: 470 (76.4%) females, mean...

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