Biopharmaceuticals safety perception in Slovakia: considerations and real-life pharmacovigilance data.

OBJECTIVES: Biopharmaceuticals improved the prognosis and quality of life of patients with chronic diseases. The aim of our study was to analyse the total reported suspected adverse drug reactions (ADR) and ADRs of reference biologicals and their biosimilars in Slovakia. METHODS: Using data from the State Institute for Drug Control database, we analysed the trends of suspected ADR submitted between 2001-2017 including the registered biosimilars and their reference biologicals: erythropoietin, filgrastim and infliximab. RESULTS: Severe suspected ADR represented 42.95 % from all the reported cases (n=13,462) over the time period 2006-2017 and 54.98 % over 2015-2017 respectively. Reports from 2015-2017 were further analysed. From 4,364 cases, 27 were associated with infliximab and one with erythropoietin. 75 % of these ADR were severe including one death. The difference between the suspected ADR for infliximab reference biological compared to the biosimilar was not statistically significant (p=0.171) after adjustment to the number of prescribed drug units. CONCLUSION: We did not find any evidence of increased risks associated with biosimilars compared to reference biologics. The spontaneous reporting system represents an inexpensive tool of reporting ADRs and should be utilized more frequently by health professionals, but even more importantly, by patients (Tab. 3, Fig. 2, Ref. 30). Text in PDF www.elis.sk Keywords: adverse drug reaction, spontaneous reporting, biopharmaceuticals, biosimilars, infliximab.

The use of antiplatelet medication in hospitalised elderly patients.

BACKGROUND: The use of antiplatelet agents is strongly recommended for the secondary prevention of ischemic events such as myocardial infarction, stroke/transient ischemic attack (TIA). OBJECTIVES: The aim of our study was to analyse the use of antiplatelet medication in patients after myocardial infarction, stroke/TIA, and patients with both conditions and to identify patient-related characteristics, which determine the use of such drugs in elderly patients. METHODS: Study sample (n=372) was derived from 2,157 patients admitted to long-term care departments of three municipal hospitals. The study included patients aged ≥65 years after myocardial infarction, stroke/TIA or both. RESULTS: Antiplatelet medications were prescribed in 54.8 % and 68.5 % of patients at hospital admission and discharge, respectively. Hospitalisation led to a significant increase in the use of antiplatelet medication in patients after myocardial infarction and in those with the combination of both events. However, in patients after only stroke/TIA, we did not find any significant difference comparing the use of antiplatelet medication at the time of hospital admission and discharge, respectively. CONCLUSION: Our study revealed that physicians are more aware of the benefits of antiplatelet medication in elderly patients after myocardial infarction or those after both myocardial infarction and stroke/TIA in comparison with patients after only stroke/TIA (Tab. 3, Ref. 32).

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

PURPOSE: The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. METHODS: Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. RESULTS: Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). CONCLUSION: Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

A commentary on a decrease in consumption of selective COX-2 inhibitors (coxibs) Comparison between Slovakia and Nordic countries.

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).

Consumption of three most widely used analgesics in six European countries.

WHAT IS KNOWN AND OBJECTIVE: Analgesics are among the most widely used drugs and there is wide intercountry variability in the rates of consumption of different analgesics. Our objective is to determine and compare patterns of analgesic consumption in the Slovak Republic and a number of other European countries. METHODS: We undertook a drug utilization study using WHO ATC/defined daily doses (DDD) methodology. Wholesale analgesic data collected by the Slovak State Institute for Drug Control were used. Utilization was calculated as DDD per 1000 inhabitants per day. Comparison with wholesale data from Czech Republic, Estonia, Finland, Norway and Denmark, published on the Internet, was made. RESULTS AND DISCUSSION: Paracetamol/acetaminophen consumption varied only a little in Slovak Republic and Czech Republic, whereas consumption in Nordic countries was significantly higher (P < 0.05) and in Estonia significantly lower. Ibuprofen consumption was significantly higher in Czech Republic and Finland. Significantly lower consumption was in Norway. The lowest consumption of ASA/aspirin was in Denmark and in Norway. The highest consumption was in Finland. WHAT IS NEW AND CONCLUSION: Effective therapy needs good prescribing and well-informed prescribers and patients. Our study highlights wide differences in analgesic consumption even among similar European countries. The basis of these differences and their potential clinical impact require further investigation.

5 most consumpted opioid analgesics in Slovakia in the year 2006--comparison to five other countries (Finland, Norway, Denmark, Spain, Australia).

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.

Modified problem-based learning in pharmacology.

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.

Current opinions on the role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease.

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.

Endothelaemia--a marker of vascular damage.

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.

Perception of drug risk in the database of Drug Information Centre in Bratislava.

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.

[Consultation activity of two Slovak centres for pharmacotherapy during pregnancy and lactation]. / Konzultacná cinnost' dvoch slovenských centier pri farmakoterapii v gravidite a laktácii.

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.

Experience with problem oriented teaching in pharmacology.

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.)

The Slovak Drug Information (Druginfo) Centre during the period 1997-2004.

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.)

Assessing skills in pharmacology in medical students.

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).

Trends in consumption of opioid analgesics in Slovak Republic during 1998-2002.

OBJECTIVE: To describe the patterns of consumption in an opioid analgesic group in Slovakia between 1998 and 2002, to determine prescription habits, and to compare the results with those from selected countries. METHODS: A drug utilization study using WHO methodology [Anatomical-Therapeutic-Chemical classification/defined daily doses (ATC/DDD)] was made. The wholesale data from the State Institute of Drug Control in the Slovak Republic and drug safety reports from the National Centre for Supervision of Adverse Drug Reaction were collected. Utilization was calculated as the DDDs per 1000 inhabitants per day. RESULTS: Consumption of opioid analgesics (ATC class N02AA-N02AX) in Slovakia was still growing during the study with dominance of tramadol. In comparison with other countries in 2001, consumption of morphine (as a representative of analyzed ATC class) in Slovakia (0.17 DDD/1000 inhabitants per day) is still very low, in contrast with Denmark, Austria or Canada (1.80, 1.61 and 1.58 DDD/1000 inhabitants per day, respectively). The collected safety reports contained only a few reported adverse reactions to the opioid analgesics. CONCLUSION: Despite recent increases, the consumption of opioid analgesics in the Slovak republic remains low. We have tried to present an overall picture of prescription of opioid analgesics in Slovakia and to focus attention on this topic.

Factors influencing the spontaneous reporting of adverse drug reactions--the experience of the Slovak Republic.

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.

Temporal situation of NSAID-related adverse drug reaction reports in Slovak Republic.

To make the drug therapy safer and more rational, it is substantial to gain sufficient amount of information concerning the perception of ADRs, especially those related to most "risky" groups such as NSAID. By viewing ADR reporting as a professional responsibility, and recognizing that the quality of submitted information, health professionals can play a major role in improving the public health. (Fig. 2, Ref. 5.)

[Are we underestimating the nephrotoxicity of drugs?]. / Nepodcenujeme nefrotoxicitu liekov?

In the submitted review the authors discuss the nephrotoxicity of drugs which is a serious danger of pharmacotherapy. Clinically it may be manifested in different ways from acute deterioration of renal functions to the picture of chronic renal insufficiency. It is particularly important to know the nephrotoxic potential of different drug groups and to ensure a careful stratification of patients. The most frequent drug groups which lead to affection of the kidneys are radiocontrasting substances, aminoglycoside antibiotics, non-steroid analgesics-antiphlogistics and ACE inhibitors. With the increasing number of transplantations the problem of nephrotoxicity of immunosuppressives is becoming important. The authors analyze in each group risk factors, the pathogenesis, clinical picture and prognosis of damage. Special emphasis is laid on adherence to preventive measures and careful monitoring of the laboratory and clinical picture, in particular in risk groups of patients as treatment of already developed nephrotoxic sequelae of pharmacotherapy is frequently difficult.

Drug information center.

One of the most important prerequisities concerning the process of selecting drugs for rational pharmacotherapy is the availability of independent information about them. The first self-existent Drug Information Center (DIC) in Slovakia was established in May 1997 at the Department of Pharmacology, School of Medicine, Comenius University in Bratislava. The organization of DIC and its activities are similar to other analogous centers in other countries. DIC provides free drugs information to all medical professionals. The majority of inquiries are from hospital physicians followed by general practitioners and staff of the University. The most frequent questions involve basic information about drugs, pharmacotherapy during pregnancy and lactation, adverse drug reactions, registration of new drugs, drug action etc.

Eradicative effect of cotrimoxazole and quinolones on non-typhoid salmonellae.

Opinions on antibiotic treatment of salmonella gastroenteritis are still different. Many authors support an opinion that antimicrobial treatment has no effect on salmonella elimination. The authors of the study have tried to prove that fluoroquinolones shorten the elimination of salmonellae and therefore they are useful not only for the treatment of salmonella gastroenteritis in immunocompromised patients to prevent sepsis and extraintestinal manifestations of the infection, but also for eradication of salmonellae in food industry workers, whose carrier state might exclude them from their work. (Tab. 3, Ref. 10.)