Characteristics of COPD patients treated with single­inhaler triple therapy in real-life clinical practice.

BACKGROUND: Inflammation associated with chronic obstructive pulmonary disease (COPD) causes narrowing of the airways and destruction of the lung parenchyma. The triple therapy (ICS+LABA+LAMA) may improve lung function, patient­reported outcomes, and exacerbation risk in a specified subset of GOLD group D patients. A better understanding of the factors leading to the single­inhaler triple therapy (SITT) prescription in real-life scenario is still an unmet need. METHODS: We assessed the characteristics of 838 GOLD group D patients treated with SITT and way of how those patients had been routinely managed before in their outpatient settings. The cross-sectional observational survey was based on an assessment of routine practice patterns and retrospective collection of anonymous medical data. RESULTS: Severe and very severe forms of airflow obstruction were experienced by 52 % and 34 % of patients, respectively. The mean number of exacerbations during the 12­month period antecedent to SITT prescription was 2.01. Before starting SITT, various combinations of COPD medications were prescribed: LABA (95 %), followed by ICS and LAMA. Compared to patients with 0-1 exacerbation, the patients with ≥2 exacerbations had higher levels of mMRC and CAT scores (2.47 vs 2.69 and 16.02 vs 19.31, respectively, both p <0.001), worse treatment adherence and higher need for rescue medication (4.7 vs 3.9 units, p=0.0011). The driver for switching the treatment to SITT was an expected improvement in lung function followed by reduction in dyspnoea and number of exacerbations. CONCLUSIONS: Despite current treatment, the burden of COPD remains significant in GOLD group D patients. The lung function, symptoms burden and exacerbation history are among the most important factors involved in the decision for stepping up to SITT with potential roles of both bronchodilator and anti-inflammatory components (Tab. 2, Fig. 9, Ref. 66).

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.

Patients attitudes towards experience with use of generics in Slovakia, performance of generic substitution.

BACKGROUND: Generic substitution of branded pharmaceuticals is a widely adopted tool among payers to achieve cost savings. The adoption and safe use of generics among consumers is predicated upon their knowledge of and attitudes toward these products. OBJECTIVES: The aims of this study were to assess patients' attitudes towards generic drugs and their experience with using generics, identify factors associated with differences in attitudes and/or experience, and discern the rate of generic substitution in Slovakia. METHODS: Two thousand questionnaires were distributed to patients via pharmacies throughout Slovakia by eleven pharmaceutical companies representing GENAS (the Slovak Generic Association). Responses were received from 1,777 persons (88.85% response rate). Demographic information of respondents was also acquired. RESULTS: Only 33.8% (600/1773) of respondents care to know about the product which they are using. Over one half (61.1%, 1084/1774) of respondents indicated no distrust in using generics, with many of them indicating a preference for a product with a lower co-payment. CONCLUSION: About 1/3 of patients care to know whether they are using generic or branded pharmaceuticals. If there is a lack of information about generics, this could inhibit the use of generics by patients and discern a rate of generic substitution (Tab. 3, Fig. 1, Ref. 18).

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.

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.

Perception of potentially inappropriate medication in elderly patients by Slovak physicians.

PURPOSE: The aim of the present study was to determine the risk perception of potentially inappropriate drug treatment of elderly patients by Slovak physicians. In Slovakia, a list of such drugs is not available. METHODS: The study sample consisted of 600 patients aged > or =65 years hospitalized at the Department of Internal Medicine in a Slovak general hospital between 1 December 2003 and 31 March 2005. The use of potentially inappropriate drugs at the time of hospital admission and discharge was compared. Potentially inappropriate drug use was defined by Beers 2003 criteria. In addition, 206 physicians were asked to mark the drugs that they considered potentially inappropriate for elderly patients out of a list provided in a questionnaire analysis. RESULTS: Out of 600 patients 20.2% and 20% were treated with at least one potentially inappropriate drug at the time of hospital admission and discharge, respectively. Hospitalization had no significant influence on the number of potentially inappropriate medicines used. The most frequently prescribed potentially inappropriate drugs were digoxin >0.125 mg/day and ticlopidine. Out of 206 responding physicians only 4.9% considered ticlopidine as potentially inappropriate for elderly patient. On the other hand, more than 20% of respondents were aware of the potential inappropriateness of amitriptyline, diazepam and chlordiazepoxide. Mentioned drugs were observed in less than 2% of study population (n = 600). CONCLUSIONS: The results of the questionnaire analysis in physicians as well as the prevalence of potentially inappropriate medication demonstrate that Slovak clinicians are aware of the risk of certain treatments in elderly patients.

[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.)

[Pharmacoeconomic profile of antibiotics used in the treatment of lower respiratory tract infections in geriatric patients]. / Farmakoekonomický profil antibiotík pouzitých v liecbe infekcií dolných dýchacích ciest u geriatrických pacientov.

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.

Cost-effectiveness analysis of switching from intravenous to oral administration of antibiotics in elderly patients.

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.)

Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers.

The standardized extract of Ginkgo biloba (EGb 761) was found not only to improve memory and aging associated cognitive deficits but also to exert beneficial effects on mood. An antistress action of the extract has been suggested but not directly proven. The present study was aimed to evaluate the effects of EGb 761 on salivary cortisol and blood pressure responses during stress in healthy young volunteers (n = 70) in a double blind placebo controlled design. A stress model involving a combination of static exercise (handgrip) and mental stimuli was used. Single treatment with EGb 761 (120 mg) reduced stress-induced rise in blood pressure without affecting the heart rate. Salivary cortisol responses showed differences with respect to the gender and the time of day of the stress exposure, with the activation only in male subjects in the afternoon. This activation was absent if they were treated with EGb 761. The performance in a short memory test with higher scores achieved by women remained unaffected by EGb 761 treatment. Thus, this study provides evidence that EGb 761 has an inhibitory action on blood pressure and it may influence cortisol release in response to some stress stimuli.

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.

[The effect of chronic acidosis on the activity of renal glutamate decarboxylase and GABA-transaminase]. / Vplyv chronickej acidózy na aktivitu oblickovej dekarboxylázy glutamátu a GABA-transamináz.

Chronic acidosis evoked by a 7-day application of ammonium chloride in concentration of 2% increased the activity of glutamate decarboxylase (GAD) in renal homogenates of rats to approximately 160%. The enzyme activators, chlorides and adenosine triphosphate influenced in varying measures the GAD activity in renal homogenates of both controlled and acidotic animals. Whilst ATP was gradually loosing the activating effect, chlorides preserved it. The renal GAD is firmly bound on insoluble structures. The increase in GAD activity due to acidosis was accompanied by increasing permanence of this bind. After the substitution of ammonium chloride by drinking water, the return of the increased GAD activity to previous normal values lasted 7 days, whilst apparent normalization of the weight of experimental animals reoccurred on the first day. Subfractionation of the crude renal mitochondrial fraction by use of enzyme markers localized GAD in mitochondria. In renal homogenates the activities of GABA-transaminases were assessed. GABA-alpha-ketoglutarate transaminase was 5x more active than GABA-pyruvate transaminase. Acidosis resulted in augmentation of both transaminases--the first to 130%, the second to 160%. (Tab. 5, Fig. 3, Ref. 25.)

[Glutamic acid decarboxylase in the brain, pancreas and kidneys. Comparison of its properties]. / Dekarboxyláza kyseliny glutámovej (GAD) z mozgu, pankreasu a obliciek. Porovnanie niektorých vlastností.

Comparisons of soluble and bound GAD activities in brain, pancreas, and kidneys were performed. In all three organs GAD was present in three forms: soluble GAD; GAD, the solubility of which was achievable by means of CHAPS detergent; and GAD, refractory towards the detergent affect. The activity of these three GAD fractions, each belonging to a different cellular compartment, proportionally differed. The ratio of free, bound, and irreversibly bound activity expressed in percentage was 63:21:15 in the brain, and 14:40:36 in the pancreas. In coincidence with the occurrence of autoantibodies to GAD from the brain under the condition of SMS, and that from the pancreatic beta-cells under the condition of IDDM, it is supposed that the conditions favourable for the origin of the immune response are rendered by GAD bound in membranes. In kidneys the proportions of free (15%) and bound GAD (29%) are complicated by until now unassessed factors, since their isolation from the free, eventually bound GAD causes an activity waste of 50% which supervenes following the homogenate separation by the use of centrifuge. Effect of ATP and chlorides displays both, different and common properties of GAD from the mentioned three organs. ATP inhibited the brain GAD and the renal supernatant GAD, whereas it activated GAD from the homogenate and sediment of the kidneys and the pancreatic GAD. Chlorides inhibited the brain and pancreatic GAD and activated the renal GAD. (Fig. 8, Tab. 1, Ref. 16.).

The influence of hypoxia on the formation of amino acids from oxidized substrates in the rat brain in vivo.

Hypoxia can influence the development of pathological processes in the brain not only through the decrease of oxidative phosphorylation but also by synthesis and release of excitatory amino acids and GABA. We studied the influence of hypobaric (pO2 8.6 kPa) and normobaric hypoxia (pO2 5.27 kPa) on the transformation of U-14C glucose and 2-14C acetate into some amino acids connected with the tricarboxylic cycle. Hypobaric hypoxia and normobaric hypoxia have different effects on metabolic processes in neuronal and glial cells. The formation of the studied amino acids from U-14C glucose (neuronal compartment) was more decreased than the formation of amino acids from 2-14C acetate (glial compartment). This could be a consequence of higher sensitivity of neuronal than glial mitochondria to oxygen deficit or a result of uncoupling of amino acid formation in neurones. An unchanged synthesis of glutamine from acetate in glial cells during hypoxia may result in a protective metabolic effect.

[The effect of ethanol on gamma-aminobutyric acid in the brain]. / Vplyv etanolu na kyselinu gamaaminomaslovú (GABA) v mozgu.

The effect of acute and chronic ethanol administration on the level of gamma-aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated. The level of GABA rose both after acute and chronic ethanol administration. In chronic experiments also the level of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system.

The effect of Ca+ free medium on the two different tricarboxylate cycles in the rat brain cortex slices.

The authors studied the effect of calcium-free saline-glucose medium on labelled amino acid and [14C]CO2 synthesis from U-[14C]-glucose and 1-[14C]-acetate in rat brain cortex slices. Respiration was stimulated parallel with increased synthesis of labelled amino acids and of [14C]CO2 from glucose to [to 150 % and 170 % respectively]. Specific glutamate, aspartate and neutral amino acid activity rose, GABA and glutamine were unaffected. Amino acid synthesis from 1-[14C]-acetate was inhibited [58%], while [14C]CO2 release was unchanged. This indicates that oxygen consumption via the tricarboxylase cycle associated with the small glutamate pool [and probably localized in the glia cells] did not alter in calcium-free medium, although conversion to amino acids was impaired.

The effect of excess K+ on two different tricarboxylate cycles in rat brain cortex slices.

The authors compared, in rat brain cortex slices, the oxidation of labelled glucose and acetate and the conversion of these precursors into amino acids during incubation in control salt-glucose medium and in medium with 47 mM K+, with the aim of determining with which of the two determinable tricarboxylate cycles raised oxygen consumption is associated in the presence of excess K+. Under the experimental conditions it was found that from U-[14C]-glucose more than double the amount of [14C]-CO2 was formed and that the rate of [14C] incorportation into the amino acids was likewise roughly doubled. This is indicative of activation of processes in the tricarboxylate cycle associated with the large glutamate pool. Incorporation from 1-[14C]-acetate into the total amino acids was not affected. Specific activity in glutamate and asparate was more than doubled, while glutamine specific activity fell to less than half. [14C]-CO2 production fell to 65%. This shows that the tricarboxylate cycle associated with the small glutamate pool, which is probably localized in the glia cells, did not participate in raised oxygen consumption in the presence of excess K+.