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Capicua (CIC)-rearranged sarcomas are an aggressive subset of undifferentiated round cell sarcomas. CIC::DUX4, the proto-typical CIC fusion oncoprotein is associated with rapid clinical progression and chemotherapy resistance leading to poor clinical outcomes. Recent studies have identified additional CIC fusions (CIC::NUTM1, CIC::FOXO4, and CIC::LEUTX) that largely retain CIC-binding specificity but leverage C-terminal binding partners (NUTM1, FOXO4, and LEUTX) to potentially activate transcriptional programs that drive oncogenesis. Moreover, the recent development of preclinical models to study CIC::DUX4 sarcoma have advanced our understanding of the underlying biological mechanisms and uncovered key dependencies that can be translated into rational therapies. In this review, we will highlight these recent advancements in CIC-rearranged sarcoma biology with a vision for clinical translation to improve patient outcomes.

CIC-DUX4 rearrangements define an aggressive and chemotherapy-insensitive subset of undifferentiated sarcomas. The CIC-DUX4 fusion drives oncogenesis through direct transcriptional upregulation of cell cycle and DNA replication genes. Notably, CIC-DUX4–mediated CCNE1 upregulation compromises the G1/S transition to confer a dependence on the G2/M cell cycle checkpoint. Through an integrative transcriptional and kinase activity screen using patient-derived specimens, we now show that CIC-DUX4 sarcomas depend on the G2/M checkpoint regulator WEE1 as part of an adaptive survival mechanism. Specifically, CIC-DUX4 sarcomas depended on WEE1 activity to limit DNA damage and unscheduled mitotic entry. Consequently, genetic or pharmacologic WEE1 inhibition in vitro and in vivo led to rapid DNA damage–associated apoptotic induction of patient-derived CIC-DUX4 sarcomas. Thus, we identified WEE1 as a vulnerability targetable by therapeutic intervention in CIC-DUX4 sarcomas.

Capicua (CIC)-rearranged sarcomas are an aggressive subset of undifferentiated round cell sarcomas. CIC::DUX4, the proto-typical CIC fusion oncoprotein is associated with rapid clinical progression and chemotherapy resistance leading to poor clinical outcomes. Recent studies have identified additional CIC fusions (CIC::NUTM1, CIC::FOXO4, and CIC::LEUTX) that largely retain CIC-binding specificity but leverage C-terminal binding partners (NUTM1, FOXO4, and LEUTX) to potentially activate transcriptional programs that drive oncogenesis. Moreover, the recent development of preclinical models to study CIC:: DUX4 sarcoma have advanced our understanding of the underlying biological mechanisms and uncovered key dependencies that can be translated into rational therapies. In this review, we will highlight these recent advancements in CIC-rearranged sarcoma biology with a vision for clinical translation to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aim: Adverse effects (ADRs) of non-steroidal anti-inflammatory drugs (NSAIDs) represent a public health problem. To decrease the negative effect on the population, an improvement of risk awareness is crucial. We aimed to evaluate the risk perception and the use of NSAIDs in South Dakota in comparison with Slovakia and Greece., Method: A structured questionnaire evaluating NSAID use in 185 patients in a hospital in South Dakota., Results: 95.7 % of respondents reported the use of analgesics. On 1-10 visual analogue scale, perceived risk of NSAIDs was 4.27±2.46, similar to Greece (4.36±2.41, p=0.360), but significantly higher than in Slovakia (3.8±1.9, p=0.038). Only 12.4 % were familiar with gastrointestinal ADRs and only 1.1 % were aware of cardiovascular risk. Although 57.8 % were informed about ADRs by their doctor or pharmacist, only 33.0 % were informed spontaneously, without actively asking. Providers in South Dakota were informing patients spontaneously more often than in Slovakia (15.9 %, p≤0.001) and on par with Greece (36.3 %, p=0.631)., Conclusions: Public awareness about NSAID risk is dangerously low. Only a third of providers are informing patients about possible risks spontaneously (Tab. 6, Ref. 15) Keywords: non-steroidal anti-inflammatory drugs, risk perception, adverse effects, cardiovascular risk, gastrointestinal risk.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics worldwide in different syndromes. There is a relevant evidence about NSAIDs various adverse effects (AEs) on gastrointestinal, cardiovascular, renal, pulmonary, nervous systems. Many of these problems are preventable with respects to appropriate patient´s risk perception., Objectives: The main goal of our study was to examine drug risk perception with relation to participation factors as comorbidities in patients., Methods: A structured questionnaire was delivered to 124 patients hospitalized at Department of Internal Medicine in a selected General Hospital in Greece. Data were evaluated using a descriptive statistics., Results: Low awareness of NSAID risk was recorded, with 45.16 % of respondents unaware of any particular AEs. Lack of this knowledge appears to be attributed to low communication of physicians and pharmacists with patients about possible risk from comorbidity, over half of respondents (55.8 %) had history of hypertension, and 25.9 % were diabetics, which would increase the risk of NSAID therapy., Conclusion: Our study revealed a restricted knowledge about risk of NSAIDs in the studied population and showed some important data related to the presence of comorbidity in patients, which could potentiate the risk of cardiovascular AEs (Fig. 5, Ref. 22).

Purpose: The aim of our work was to analyze utilization patterns in Slovakia and Nordic countries and to determine coxib risk perception among medical professionals., Methods: The consumption of coxibs in Slovakia during 1999-2009 was analyzed. Data were obtained from the State Institute for Drug Control in SR. Obtained results were compared to data based on annual health statistics in Denmark, Finland and Norway. General Practitioners were asked on a perceived risk., Results: We observed an increase of consumption in first years, followed with a marked decrease after year 2004. Slovak consumption was very small. Coxibs represented in Slovakia only a small part of totally prescribed non-steroidal anti-inflammatory drugs. They constituted only 1.44 % in the year 2003, whereas in Norway 41.2 %. 14 % of respondents (n=570) marked coxibs to be the safest analgesic drug., Conclusion: Published data show that consumption of coxibs (rofecoxib was linked with serious thrombotic cardiovascular adverse effect) fall down markedly. Consumption data from 1999 until 2009 from Slovakia and three Nordic countries showed significant differences (p<0.001). During the observed period, the utilization of coxibs in Slovakia was very small - a possible explanation is new drug, higher prize, doctor's habits (Tab. 2, Fig. 1, Ref. 11).

Objectives: The aim of our study was to analyse analgesic risk perception and then to compare analgesic drug choice among general practitioners., Method: The structured questionnaire was used and completed during continuous medical education lectures. Series of targeted open or close questions and visual analog scale (VAS) to determine drug risk perception were used. Slovak general practitioners attending continuous medical education lectures during 2004-2005 were invited to participate in the study. Group 1 consisted of respodents from Bratislava (capital city of Slovakia, n = 245) and group 2 consisted of general practitioners from 3 other cities (middle and eastern Slovakia, n = 325). Data were compared to reported adverse drug reactions., Results: Quarter of doctors 25.3% (n = 62), (25.2% (n = 82) respectively), considered non-steroidal anti-inflammatory drugs to be the safest group of analgesics. Gastrointestinal damage in general was perceived as most common adverse drug reaction. 72.41% (75.94% respectively) of respondents considered analgesics as exactly or probably danger. Perceived drug risk labeled on VAS was 4.23 (SD 1.52), (3.22 (SD 2.19) respectively) (p < 0.05). Total number of reported adverse drug reactions in years 1998-2002 was 3249, 412 were related to analgesic use. Specific organotoxic adverse drug reactions (nephrotoxicity, etc.) were reported rarely., Conclusion: The actual perception of analgesic risk in Slovakia seems to be generally inadequate. We found only a low support of spontaneous adverse drug reactions reporting to the national monitoring system (Tab. 1, Fig. 2, Ref. 11).

Objective: The aim of this study was to determine differences between PBL as compared to modified PBL with special focus on acquiring EBM principles., Methods: Two groups consisted of total 152 students (139 respectively). The use of EBM principles means integrating individual expertise with the best available external clinical evidence by using available data sources and national guidelines., Conclusion: Our findings suggest that modified PBL with extended EBM approach could be superior to "classical" PBL (Fig. 3, Ref. 29). Full Text (Free, PDF) www.bmj.sk.

Objectives: The aim of the study was to identify and confront the opinions of both patients and general practitioners on their relationship., Methods: Our questionnaire was designed according to the target of our study--to analyse the communication between the GP and the patient as well as the adherence to the treatment procedures--in the group of 100 GPs and 500 patients., Results: The response rate was 95% in GPs and 86.6% in patients. Totally, 88% of patients and 52% of GPs were convinced that the compliance with the treatment and the trust to the GP are related., Conclusions: Non-compliance is a frequent reason for the patient's unsatisfying response to the therapy. A professional approach to this problem is an essential precondition of an increased quality of health care and an increased patient's satisfaction without requirements of health care system for additional financial resources (Tab. 1, Fig. 1, Ref. 12).

Introduction: Opioid analgesics are drugs of choice in the treatment of moderate and severe malignant or noncancer pain. Consumption data helps us to evaluate the status of country's public health., Methods: We analysed the consumption of opioid analgesics from ATC class N02A in Slovakia in the year 2006 and compared it with five other countries -- Finland, Norway, Denmark, Spain and Australia. We then calculated drugs that accounted for 90% of the total volume of DDDs in the year 2006., Results: Slovakia showed a dominance of tramadol consumption that constituted three quarters of the total group consumption. Tramadol is the commonest consumed opioid analgesic in all observed countries (in Norway it constituted only 35% of total group consumption, whereas in Slovakia it was 72%)., Discussion: Opioid consumption in Slovakia is increasing, but comparison with the Nordic countries, Spain and Australia showed a significantly lower consumption. Exception is tramadol with the highest consumption in Slovakia., Conclusion: Observed trends in consumption indicate a well known accent of the Nordic countries on treatment of pain. Opiod consumption in Slovakia continues to stay low (Tab. 1, Fig. 1, Ref. 10). Full Text (Free, PDF) www.bmj.sk.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) belong to most frequently used drugs worldwide. NSAIDs belong to the family of drugs that represent the biggest drug risk as to the number of adverse drug reactions (ADRs), as well as to the number of deregistered drugs., Methods: We analysed the whole consumption of NSAIDs from ATC class M01 in Slovakia during 1996-2007., Results: Most frequently used NSAIDs in Slovakia were ibuprofen and diclofenac. There was a marked increasing trend in piroxicam, meloxicam, ibuprofen and especially nimesulide medicines., Conclusion: Prescription habits of doctors in Slovakia reflect the drug risk only partially, nevertheless the total consumption of dangerous medicines is decreasing and substances with safer profile remain being more used. In the prescribing process the patients' risk factors together with the differences in drug characteristics should be considered. Nevertheless some of these drugs are OTC, and their consumption is strongly influenced by pharmacists and advertisement (Tab. 2, Fig. 1, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Background: The phenomenon called aspirin resistance is being intensively discussed., Methods: To evaluate the biochemical aspirin response, the method of urinary 11-dehydro TXB2 levels measurement was used. Quantitative detection of TXB2 in urine was determined by competitive enzyme immunoassay, using human Thromboxane B2 ELISA-kit. We investigated the urine samples from 69 patients., Results: The mean urinary levels of 11-dehydro TXB2 were significantly lower in patients in the primary and secondary types of aspirin prevention comparing with the control group of patients not taking aspirin. The difference in thromboxane concentrations between the two groups of patients taking aspirin did not reach statistical significance. Our results did not show significant differences in the biochemically measured aspirin response when comparing diabetics with non-diabetics. Similarly, the observed tendency to higher thromboxane levels in women did not show to be significantly different from men., Conclusion: Our pilot study did not show any significant differences among patients at different cardiovascular risk. Since there is currently no standard laboratory method to detect aspirin non-responders available, the term aspirin resistance remains controversial and requires further research. Every effort should be done to improve patients' compliance and to prevent clinically relevant interactions of aspirin with ibuprofen. The elimination of these two factors as was the case in our study may provide better efficacy of the antithrombotic prevention by aspirin (Fig. 2, Tab. 4, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

Background: Chronic obstructive pulmonary disease (COPD) is one of the main cases of mortality and morbidity of population worlwide. In spite of enormous efforts there are not pharmacological agents evidently influencing natural course of disease available. Besides looking for new drugs influencing the long term outcome of patients with COPD, there is also running the process of reevaluation of the role of several already established drug groups., Methods: Through the use of recent knowledge and results from large-scale clinical studies as well as metaanalyses we give a view on action of inhaled corticosteroids in the pathophysiological mechanisms of COPD and complex summary of their role in the therapeutic management of the disease., Conclusion: Contrary to systemic corticosteroids, agreement regarding usage of inhaled corticosteroids necessary by acute exacerbations of disease has not been reached yet. Recent meta-analyses of the long-term clinical studies have clearly demonstrated that inhaled corticosteroids could pose with ability of slowing down the progressive deterioration of lung functions and lead to the prolongation of life in broad population of patients with COPD. Benefit of treatment insists in decrease of frequency and severity of exacerbations, mildering symptoms, improving overall health state as well as exercise tolerance in patients with COPD. Clinical relevant is also reduction of the number of hospitalizations and mortality related to progression of COPD (Tab. 2, Ref 45) Full Text (Free, PDF) www.bmj.sk.

Objectives: The aim of the study was to determine the amount of circulating endothelial cells (CECs) in patients with an advanced cardiovascular (CV) disease, compare the values with a control group and finally to ascertain if there are statistically significant differences within the studied patient groups., Background: Endothelaemia has been intensively studied as a marker of vascular injury. Clinical studies have demonstrated an increased endothelaemia in patients at high CV risk but also in certain non-cardiovascular disorders. Its possible usage in the diagnostics of the acute coronary syndrome and for CV risk assessment needs further investigations., Methods: Thirty six hospitalized patients were studied. Quantitative measurement of endothelaemia was performed by the method developed by J. Hladovec. It is based on ECs counting in Bürker's chamber after their isolation with platelets and the removal of the latter by an addition of adenosine-diphosphate., Results: The mean baseline endothelaemia was significantly higher in patients with increased cardiovascular risk when compared with the control group (1.38 +/- 0.899): ACS (4.9 +/- 1.59, p < 0.05) and PAOD (3.74 +/- 0.61, p < 0.05). When comparing the mean endothelaemia values in patients with PAOD before (2.67 +/- 0.86) and after (3.88 +/- 0.77) surgery, a significant increase of endothelaemia was observed (p < 0.05)., Conclusion: Our pilot study, though limited by a relatively small number of patients, proved a significant increase of endothelaemia in patients at high CV risk, which is consistent with other available data. The introduction of newer specific methods based on immunomagnetic principles may provide a wider use of endothelaemia measurement in clinical settings (Fig. 3, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Objective: The aim of the presented study was to analyse the types and quantity of inquiries received at Drug Information Centre in Bratislava during the period from May 1997 to May 2006. The study analyses also the profile of the users of the latter centre with focus on the perception of drug risk, adverse drug reactions, and drug interactions., Background: The Drug Information Centre (Druginfo) was established in Slovak Republic as part of the Department of Pharmacology in May 1997. In 2002 Druginfo became a member of International Register of Drug Information Services of the Society of Hospital Pharmacists of Australia. Druginfo provides voluntary free of charge drug information for healthcare professionals., Methods: Statistical processing of all inquiries received at Druginfo during a 10-year period focused on the aspect of drug risk perception., Results: 867 inquiries were received in total. The most frequent inquiries came from hospital teaching clinics in Bratislava. Questions concerning pregnancy/lactation (25 %), adverse drug reactions (16 %), basic information about drugs (14 %) and interactions (13 %) were asked most frequently., Conclusion: The types of inquiries and inquirers using the service are generally similar to those recorded at many others Druginfos within Europe and USA. The number of questions is lower than in other centres. Druginfo in Bratislava has a very important role in providing independent drug information (Tab. 1, Fig. 8, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

The aim of the one-year prospective study was to estimate the prevalence of non-steroidal anti-inflammatory drugs using in patients with symptomatic gastroduodenal ulcers, the upper gastrointestinal bleeding and perforation (PUB--perforation, ulcer, bleeding). Among of 326 patients with PUB, prevalence of non-steroidal anti-inflammatory drugs using was 60%. In the group of 194 patients with non-steroidal antiinflammatory drugs induced PUB, 49% patients took aspirin, 38% non-aspirin non-steroidal anti-inflammatory drugs and 13% their combination. Low dosing aspirin (daily dosis < or =200 mg) was associated with PUB in 21% of patients. Age higher than 60 years and women had statisticaly signiticant higher prevalence of non-steroidal anti-inflammatory drugs induced PUB.

Endothelial dysfunction may belong to negative consequences of stress exposure accompanied by activation of several stress systems including the hypothalamic-pituitary-adrenocortical (HPA) axis. The present experiments were aimed at testing the hypotheses that i) immobilization (IMO) stress results in sustained increase in endothelaemia for 24 h and that ii) pentoxifylline, a drug with endothelium protective properties, attenuates the rise in endothelaemia and HPA axis activation in female rats as shown previously in males. Circulating endothelial cells increased immediately after the IMO for 2 h, returned back to control levels at 12 h and increased again at 24 h. Stress-induced rise in adrenocorticotropic hormone (ACTH) and corticosterone levels was particularly high immediately after the IMO. Pretreatment with pentoxifylline (20 mg/kg subcutaneously for 7 days) attenuated the rise in endothelaemia and adrenal corticosterone measured at 24 h following IMO. Plasma levels of ACTH and proopiomelanocortin gene expression in the anterior pituitary were not affected by pentoxifylline treatment. The present results indicate that IMO stress in female rats induces a biphasic rise in endothelaemia early at the time of stress exposure and than 24 h thereafter. Based on these data and our previous study we can conclude that intensive stress has a negative influence on endothelial cells in both sexes and no gender differences seem to be present in the protective action of pentoxifylline.

Background: In our paper we present analysis based on number and structure of consultations concerning drug used in pregnancy and lactation in the Drug Information Centre in Bratislava and at the Department of Clinical Pharmacology in Nitra during period 2000 to 2003., Methods and Results: In both centres the questions related to pregnancy and lactation represented the significant part of total sum of the requested information. Vast majority of consulted drugs belonged to C category concerning FDA pregnancy drug risk classification. In these drugs animal studies have revealed a risk, but studies in pregnant women were not available and thus the drugs had limited applicability from view point of safety. Decisions of consultants regarding drug use were based on the availability of information sources. A serious problem is the evaluation of retrospective drug risks in cases of drugs administered before pregnancy was confirmed., Conclusions: The evaluation of drug risk in fertile age, especially in early pregnancy, long-term drug administration during pregnancy and lactation becomes indispensable within professional field of clinical pharmacy and pharmacology in developing local teratogen surveillance system.

Background: Indication-based, in comparison to diagnoses-based, drug utilization studies in children are scarce in the literature., Aim: To determine the adequacy of the prescriber's indications for specific drug treatments compared to the current literature in five different European countries; and to show the possibilities of performing indication-based drug utilization studies., Design: a descriptive, cross-sectional, international study., Patients and Methods: Randomly selected sample of 12,264 paediatric outpatients seen in consultation rooms attended by paediatricians or general practitioners. Data on patient demographics, diagnoses, and pharmacological treatment, with therapeutic indications for each drug, were collected in pre-designed forms. Diagnoses and indications were coded using the ICD-9 and drugs according to the ATC classifications., Results: Indications were registered for every drug prescribed in all locations. Antibiotic indications considered incorrect (common cold, upper respiratory tract infections, viral infections, general symptoms or "not specified") accounted from 24.1% of the total antibiotics prescribed in Tenerife to 67.4% in Slovakia. Incorrect indication of first-choice antibiotics prescribed in acute otitis media and tonsillitis ranged from 28.9% of total antibiotics use in Russia to 75.4% in Tenerife. Correct antibiotic indications ranged from 23.4% of total antibiotics used in Slovakia to 65.7% in Tenerife. Aspirin use in febrile viral conditions was detected mainly in Toulouse and Russia., Conclusion: The main areas for improvement detected were high use of mucolytics, prescription of aspirin in potential or established viral infections, overuse of antibiotics and identification of specific patterns of incorrect antibiotic prescription and clinical entities associated with each location.

The paper aims to evaluate the pharmacoeconomic profile of antibiotics (ATB) used in the treatment of lower respiratory tract (LRT) infections and thus contribute to rationalization of therapeutic procedures. Of 2870 patients hospitalized at the Geriatric Clinic of the Medical Faculty of Comenius University from 1 January 1999 to 31 December 2001, 189 patients with acute infections of the LRT were included in the retrospective study. For pharmacoeconomic evaluation, cost effectiveness analysis was employed, the principal parameter of which, cost effectiveness coefficient, was the ratio of the price of ATB treatment in Slovak crowns (SK) and the criterion of effectiveness (E), the number of asymptomatic days in a month. The authors separately evaluated ATBs administered perorally (p.o.); intravenously (i.v.), and sequentially, and they also compared i.v. and the corresponding sequentially administered ATBs. Statistical comparison revealed significant differences in the prices and cost effectiveness coefficients of individual alternatives of ATB treatment. Employed ATBs did not significantly differ in the criteria of effectiveness. According to the cost effectiveness coefficient (SK/asymptomatic day), fluoroquinolones were less expensive (median price/E: pefloxacin: p.o. 19.3; i.v. 29.1; sequentially administered 26.0, and ciprofloxacin: p.o., 14.7, i.v., 54.1, sequentially administered, 31.7). Sequential administration of ATBs (ampicillin-sulbactam, cefuroxime, amoxicillin-klavulanate, ciprofloxacin) was significantly cheaper in comparison with i.v. administration. With therapeutic equivalence, the total pharmacoeconomic profile of ATB treatment depended on the price parameter. In the selection of ATB it is also necessary to consider the price of the drug.

Objectives: The aim of the presented study was to evaluate the profile of users, the number and character of questions which were received during the period May 1997-December 2004., Background: The drug information centre (Druginfo) has been established in Slovak Republic at the Department of Pharmacology in May 1997. Since 2002 Druginfo is a member of International Register of Drug Information Services of the Society of Hospital Pharmacists of Australia. Druginfo provides voluntarily free of charge drug information for healthcare professionals., Method: Druginfo receives questions addressed via phone, fax and e-mail. The questions were replied by consulting pharmacologists on duty. The data for this study were obtained from records which include list the received questions and the basic information about the questioners., Results: The Druginfo received 495 questions during the period May 1997-December 2004. Questions were mostly from hospital physicians, followed by outpatient physicians and employees of the Faculty of Medicine. The most frequent specializations of the asking physicians were internal medicine, gynaecology-obstetrics, clinical pharmacology and general medicine. The most common topic was basic information about drugs, followed by questions concerning the use of drugs in pregnancy and lactation. According to the ATC classification the questions were most often related to antiinfective drugs, cardiovascular drugs and psychiatric drugs., Conclusion: The existence of Druginfo in Slovak Republic represents a possibility of an open access to independent drug information. (Fig. 3, Ref. 11.)

The results of this pilot survey have shown the importance of evaluation of medical student knowledge in pharmacology using three independent parts of the examination. The final mark includes the results of a written test, oral examination and evaluation of seminar essay. We evaluated students with final grade A (n=76) and F (n=61) in relation to the results of tests and seminar essays. Most of the students with grade A (88.2 %) wrote the test in the upper range (90-99 %) and their seminar essay evaluations were grade A in 82.9 %. A significant correlation between the results in the test and the mark obtained in the seminar essay was found (r=0.22, p<0.05). Another group of students with grade F obtained low scores in the test (57.4 %), and a relatively large part of students got satisfactory results in test (42.6 %). In this group the quality of seminar essays was variable ranged from A to E. The evaluation showed that in students with final grade A were all three independent part of exam in agreement with final classification. The differences occurred in group of unsuccessful students who performed much better in written part than in the oral examination. The experience with the final assessment of medical student knowledge in pharmacology showed that the most important essay evaluation seems to be the oral form of exam. The results of seminar evaluations correspond satisfactory with the performance of students during the final exam and their effort may continue in diploma work, which is mandatory for all medical students (Tab. 2, Fig. 1, Ref. 2).

Pharmacology is one of the core subjects for further graduation in both preclinical and clinical area. Medical education is being performed either in the "classical" way (lecture based learning--LBL) or in a more advanced form, such as problem based learning (PBL). According to the Medline database, the interest in PBL is still increasing. At our department, the PBL has been introduced using the knowledge obtained at the the Mac Master University and University of Groningen. PBL in pharmacology requires well-qualified staff with clinical experience. A common character of PBL is the use of selected clinical cases as models and starting points to study certain topics with a student centred approach. In an interview we made on a sample of 88 students of our medical faculty in the last study year, 65.5% of them found the amount of information concerning pharmacotherapy not sufficient for their future clinical practice and 83.3% did not feel able to use the knowledge obtained. More than 90% of students did not see enough opportunities for pharmacotherapy training during clinical subject courses. These results are in support of our orientation of teaching towards the PBL. This type of teaching forces students to be active, trains their skills in communication and selection of knowledge, which is believed to enhance the long-term knowledge retention. By using the hybrid PBL-LBL model at our department we respect the principal proposal of medical education and attempt to improve skills in decision making in training of future medical doctors. (Tab. 3, Fig. 2, Ref. 13.)

Background and Aims: Polymorbidity reduces the survival of elderly patients with pneumonia. The aim of the proposed study was to identify factors determining mortality in such patients., Methods: From January 1, 1999 to December 31, 2001, 2870 patients were admitted to the Clinic of Geriatric Medicine, Faculty of Medicine, Comenius University, Bratislava. From these, 199 patients treated for pneumonia (average age +/- SD 79.7 +/- 7.6 yr) were assigned to a retrospective study. 112 patients recovered and 87 died. The prognostic significance of the chosen factors was evaluated by comparing their incidence between the groups of surviving and non-surviving patients., Results: Prognosis for patients with pneumonia is worsened significantly by: older age; immobilization syndrome; incontinence of urine and feces; presence of some clinical and laboratory characteristics at the time of diagnosis of pneumonia (respiratory insufficiency, absence of fever, leukocytosis); pneumonia acquired in hospital; immunosuppressive therapy and comorbid conditions (congestive heart failure, chronic renal insufficiency, anemia, hepatic, psychiatric and neoplastic diseases). According to multivariate analysis, the most significant mortality-predicting characteristics were: immobilization (odds ratio (OR) 9.36; 95% confidence interval (CI) 3.92-22.33); congestive heart failure (OR 8.26; 95% CI 3.08-22.14); immunosuppressive therapy (OR 7.47; 95% CI 2.54-21.98) and psychiatric diseases (OR 4.53; 95% CI 1.94-10.58)., Conclusions: Patients with immobilization, congestive heart failure, immunosuppressive therapy, or psychiatric diseases run a high risk of death and require intensive medical care.

The system of adverse drug reaction (ADR) monitoring in the Slovak Republic is greatly influenced by changes taking place in the current health care delivery system. Under-reporting and reporting biases due to selective ADR reporting provide very serious problems in pharmacovigilance. In the year 2001, the number of reported ADRs increased due to reports of angiotensin converting enzyme (ACE) inhibitor-induced cough; this coincided with limits being imposed on the use of angiotensin-II receptor antagonists. These factors provide an example of selective ADR reporting, deforming the quality of drug safety monitoring. They also indicate that administrative strategies can significantly affect spontaneous reporting activities., (Copyright 2003 John Wiley & Sons, Ltd.)

Objective: The aim of the introduced work was to evaluate pharmacoeconomic advantages of timely switching from intravenous to oral administration of antibiotics (ATB)., Methods: The evaluated group was selected out of 2870 patients, who were hospitalised at the Clinic of Geriatric Medicine of the Faculty of Medicine of Comenius University in Bratislava from January 1st 1999 to December 31st 2001. In our retrospective study we analysed 96 patients with community-acquired pneumonia successfully treated by ATB. In 43 of them ATB were given intravenously and in 53 the therapy was switched, i.e. the intravenous administration was used at the beginning and oral administration when the condition improved. We applied a cost-effectiveness analysis to the pharmacoeconomic evaluation. The cost-effectiveness coefficient was calculated as the ratio of ATB price (Slovak Crowns) to the effectiveness criterion (number of asymptomatic days in month)., Results: According to the cost-effectiveness coefficient, the switch therapy was significantly less expensive in all evaluated ATB (except for pefloxacin) in comparison with intravenous administration: ampicillin-sulbactam 93.9 vs 168.1; cefuroxime 90.0 vs 123.3; amoxicillin-clavulanate 74.0 vs 116.3; ciprofloxacin 31.7 vs 54.1., Conclusions: A timely switching from intravenous to oral administration of ATB in a suitable patient is an effective way to save financial resources. (Tab. 5, Ref: 21.)

Multimorbidity frequently develops in old age and it is usually accompanied with pharmacotherapy of elderly patients. The growing number of seniors and comparatively low attention given to this reality among the medical community makes the problem highly significant for the practical medicine. Solution requires in the broad medical community a deeper knowledge of gerontopharmacotherapy and of its specific features, including the pharmacodynamics and pharmacokinetics in elderly organism. Non-geriatric physicians will face in their daily clinical praxis the questions of drug interactions and undesirable general and local side effects. Moreover, some foods, beverages or preservatives can influence the pharmacological effect. Due to multimorbidity in the senescence, such problems can be linked to large geriatric syndromes (instability with downfalls, immobility, decubitus, incontinency, intellectual and sensory defects of vision and hearing).

Stress is considered to be a risk factor of several diseases. The following hypotheses were tested: (1) single exposure to an intensive stressor is followed by endothelial stimulation and/or damage to endothelial cells, (2) potential stress-induced endothelial cell damage is reduced by repeated pretreatment with pentoxifylline and (3) pentoxifylline treatment modifies neuroendocrine activation during stress reflected by changes in hypothalamic-pituitary-adrenocortical (HPA) axis function. Rats were treated with saline or pentoxifylline (20 mg/kg, s.c.) once daily for 7 days and then exposed to single immobilization stress for 20 or 120 min. In saline pretreated rats, stress exposure was followed by a rise in endothelaemia, von Willebrand factor concentrations, adrenocorticotropic hormone (ACTH) and corticosterone release, as well as by enhanced gene expression of hypothalamic corticotropin releasing factor (CRH). Stress-induced changes were reduced by pretreatment with pentoxifylline. Significant inhibition was observed in endothelaemia, plasma ACTH and corticosterone concentration in the adrenals. Thus, signs of endothelial injury as well as stress-induced hormone levels were reduced by pretreatment with pentoxifylline, although there is no evidence for a causal relationship. This protective action of pentoxifylline might be of benefit in the prevention and therapy of some stress-related disorders.

Evaluation of the consumption of antimicrobial drugs is an important component of antibiotic policy and provides a picture of rationality of treatment. In the present paper, the authors analyzed the consumption of antibacterial agents of the ATC group J01 for systemic use in out-patient practice in Slovakia in 1999-2001. The data were taken from materials of all Slovak insurance companies provided by the Ministry of Health of the Slovak Republic. The paper evaluated the total out-patient consumption of antimicrobial agents and the financial costs of antibiotic therapy, analyzed the consumption of the individual groups of antibiotics and the consumption of individual agents, and compared the found out-patient consumption with that of Finland. The DDD values in the period under study gave evidence of a high but stable consumption of antibiotics. The analysis according to the groups of antibiotics revealed the dominance of penicillins with wider spectra, penicillins sensitive to beta-lactamases, and macrolides. The evaluation of individual antimicrobial agents showed a positive tendency of the growth of amoxicillin consumption, compensated by a decrease in the consumption of less advantageous ampicillin. The comparison of the Slovak and Finnish consumptions of macrolide antibiotics showed a prevailing consumption of roxitromycin and klaritromycin in Slovakia, and azitromycin in Finland. As far as cephalosporins are concerned, the preparations of the first generation dominated in Finland, and those of the second generation in Slovakia.