Background: Cardiovascular diseases remain the leading cause of mortality in Europe, responsible for one-third of all deaths in 2021. In Hungary, the standardized death rate from cardiovascular diseases reached 722.8 per 100,000 individuals, more than double the EU average. Oral anticoagulants (OACs) play a crucial role in lowering cardiovascular mortality. The use of OACs has shifted rapidly over the past decade with the transition from vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs). Although previous studies have examined gender differences in OACs prescribing, most rely on patient-level registries and do not capture population-level exposure. Aim: To evaluate population-level trends in OACs consumption in Hungary from 2014 to 2022, stratified by age and gender, with a specific focus on detecting temporal changes in the gender gap. Method: National level data were obtained from the Hungarian National Health Insurance Fund database, which includes all reimbursed prescription medications for the entire population. Utilization was measured using the WHO's ATC/DDD methodology and expressed as defined daily doses per 1,000 inhabitants per day (DID). Linear regression was used to assess trends. Results: Total OACs use nearly doubled over the study period, increasing from 9.79 to 18.73 DID (Coeff. = 1.18, p < 0.001). VKAs use declined significantly in both genders by 41.2% in males and 47.8% in females, while DOACs use increased more than tenfold. OACs utilization was consistently higher in males. Gender differences in DOACs, initially negligible, began to widen from 2018 onward, whereas, VKAs utilization exhibited a consistently wider gender difference across all years. OACs use increased with age, peaking in the 80-84 age group. Apixaban became the most used OAC, reaching 6.11 DID in 2022. Conclusion: A marked shift from VKAs to DOACs occurred, with overall OACs use nearly doubling, with a widening gender gap in consumption of both VKAs and DOACs. Utilization was consistently higher among males and increased with age, highlighting the importance of continued monitoring to ensure effective and evidence-based anticoagulant use.

Background Oral anticoagulants (OACs) are commonly used to prevent and treat thromboembolism and stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Vitamin K antagonist (VKAs) and direct oral anticoagulant (DOACs) therapies are challenging because of the possible risk of bleeding. Patient education by pharmacists could be beneficial for reducing the risk of adverse effects and improving therapeutic outcomes. Objective This scoping review aimed to investigate the outcomes of pharmacist-led patient education interventions regarding VKAs and DOACs therapies. Method Three databases (PubMed, Web of Science, and Scopus) were used following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines to identify articles published between January 1, 2008, and December 31, 2024. The data were synthesized using Rayyan AI. Results A total of 1102 records were identified. After title and abstract screening, 77 studies were selected for full-text review, and 57 articles were ultimately included. The percentages of studies that examined VKAs, DOACs, and both (OACs) were 66.7 %, 19.3 %, and 14.0 %, respectively. At least one statistically significant outcome was detected in 81.6 % (31 out of 38) of the studies on VKAs, 36.4 % (4 out of 11) of the studies on DOACs and 50 % (4 out of 8) of the studies on OACs. Conclusion This review revealed that pharmacist-led patient education was particularly effective in cases of VKAs, while the outcomes in cases of DOACs were modest. Moreover, while the role of pharmacists in patient education on VKAs has been widely studied, limited research has focused on the effect of pharmacist-led education on DOACs.

Abstract Background: Asthma is a chronic inflammatory disease of the respiratory tract that significantly impacts daily activities and quality of life. Asthma exercise is a nonpharmacological approach to asthma management. The effects of asthma exercise on interleukin-17 (IL-17) and indoleamine 2,3-dioxygenase (IDO) levels remains understudied. The effects of asthma exercise on IL-17 and IDO levels were investigated. Methods: This study included 39 participants with mild-to-moderate persistent asthma. Participants engaged in 60 minute of asthma exercise four times a week for 2 months. IL-17 and IDO levels were measured in peripheral blood mononuclear cells (PBMCs) stimulated with the house dust mite allergen Dermatophagoides pteronyssinus using ELISAs. Skin prick tests were conducted using Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis. Results: IDO levels (p-value= 0.03) increased significantly and IL-17 levels decreased significantly (p-value= 0.004) after asthma exercise. However, no significant correlation was found between the decrease in IL-17 and the increase in IDO (p-value = 0.09). Conclusion: Exercise suppresses immune responses in atopic asthma induced by house dust mite allergens. Thus, exercise is a promising therapeutic approach for atopic asthma. The effects of exercise on IDO and IL-17 levels highlight the potential of exercise to alleviate asthma-related inflammation and airway hypersensitivity.Further research is needed to understand the underlying mechanisms and optimize asthma management strategies.

Background The prevalence of diabetes is increasing, and several new drug groups have been authorized and used successfully in the treatment of diabetes, while older drug groups are still in use. Our aim was to assess the utilization tendencies and regional differences in antidiabetic medication consumption in Hungary between 2015 and 2021 and to identify the possible determinants of regional differences in antidiabetic medication use.Methods For this retrospective drug utilization study, yearly wholesale database was used, which provides total coverage for ambulatory antidiabetic drug sales in Hungary, including both reimbursed and non-reimbursed medications. Data were expressed as Defined Daily Dose per 1000 inhabitants per day (DDD/TID), percentage of total use and the ratio of the highest and lowest utilization values among the counties (max/min ratio). To assess the potential reasons for regional differences in antidiabetic drug use, we analyzed the associations between regional drug utilization data and possible determinants.Results The total national antidiabetic medication use has increased by 7.6% and reached 94.8 DDD/TID in 2021. Regarding antidiabetic subgroups, the use of metformin and novel antidiabetics (DPP4Is, GLP1As and SGLT2Is) and their combinations increased in all counties, while sulfonylurea consumption decreased, and insulin use was stable. In 2021, 19.2-24.1% of the total antidiabetic medication consumption was novel antidiabetics, 39.1-47.2% metformin, 14.8-25.8% sulfonylureas and 23.6-30.5% were insulins. Regional differences in antidiabetic medication consumption were considerable mainly in the case of GLP1As (max/min ratio:3.00), sulfonylureas (2.03) and SGLT2Is (1.92) in 2021. The association between antidiabetic medication use and possible determinants was confirmed in the case of unemployment rate and sulfonylurea use, the number of public medical card holders per ten thousand inhabitants and human insulin and sulfonylurea use. GLP1As were the only antidiabetic drug group that did not correlate with any of the investigated factors.Conclusions Although novel antidiabetic drug use was growing dynamically in Hungary, sulfonylurea use is still considerable. Differences in antidiabetic drug consumption were substantial between the regions.

The COVID-19 pandemic and related restrictions have potentially impacted the use of antibiotics. We aimed to analyze the use of systemic antibiotics (J01) in ambulatory care in Hungary during two pandemic years, to compare it with pre-COVID levels (January 2015-December 2019), and to describe trends based on monthly utilization. Our main findings were that during the studied COVID-19 pandemic period, compared to the pre-COVID level, an impressive 23.22% decrease in the use of systemic antibiotics was detected in ambulatory care. A significant reduction was shown in the use of several antibacterial subgroups, such as beta-lactam antibacterials, penicillins (J01C, -26.3%), and quinolones (J01M, -36.5%). The trends of antibiotic use moved in parallel with the introduction or revoking of restriction measures with a nadir in May 2020, which corresponded to a 55.46% decrease in use compared to the previous (pre-COVID) year's monthly means. In general, the systemic antibiotic use (J01) was lower compared to the pre-COVID periods' monthly means in almost every studied pandemic month, except for three months from September to November in 2021. The seasonal variation of antibiotic use also diminished. Active agent level analysis revealed an excessive use of azithromycin, even after evidence of ineffectiveness for COVID-19 emerged.

BACKGROUND:Opioid use is well documented in several countries: some countries struggle with overuse, whereas others have almost no access to opioids. For Europe, limited data are available. This study analysed Hungarian opioid utilization in ambulatory care between 2006 and 2020.METHODS:We obtained national drug utilization data on reimbursed opioid analgesics (ATC code: N02A) from a national health insurance database for a 15-year period. We investigated utilization trends, using three volume-based metrics [defined daily dose per 1000 inhabitants per day (DID), oral morphine equivalent per 1000 inhabitants per day, packages dispensed per 1000 inhabitants per year]. We stratified data based on administration routes, analgesic potency and reimbursement categories.RESULTS:Total opioid utilization increased during the study period according to all three metrics (74% in DID) and reached 5.31 DID by 2020. Upward trends were driven by an increase both in weak and strong opioid use (79% vs. 53%). The most commonly used opioids were fentanyl (in the strong category; 0.76 DID in 2020) and tramadol (in the weak category; 2.62 DID in 2020). Overall, tramadol was also the most commonly used opioid throughout the study period. Oral administration of opioid medications was dominant. Based on reimbursement categories, musculoskeletal pain was becoming a more frequent indication for opioid use (1552% increase in DID), while opioid use for cancer pain declined significantly during the study period (-33% in DID).CONCLUSIONS:Our low utilization numbers might indicate underuse of opioid analgesia, especially for cancer pain.SIGNIFICANCE:This study was one of the recent opioid utilization studies using three volume-based metrics, covering a long time period. To our knowledge, this was also the first national, population level study describing opioid utilization in Hungary. National opioid utilization data suggested not an overuse but rather an underuse of opioid analgesics in a developed, Central European country.

Background: The elderly use antibiotics frequently due to their increasing infection susceptibility. Given the high and increasing proportion of elderly in the population, their antibiotic use is substantial. Objective: This study aimed to compare antibiotic use in the elderly in the ambulatory care sector between Hungary and Sweden. Methods: This retrospective, descriptive, cross-national, comparative study included antibacterial use data from the Hungarian National Health Insurance Fund and the Swedish eHealth Agency. Antibiotic use (anatomical therapeutical chemical: J01) was expressed as the number of prescriptions/1000 inhabitants/year or month and was further stratified by age and sex. Results: Antibiotic exposure was higher in the Hungarian elderly population (649.8 prescriptions/1000 inhabitants/year) compared to its Swedish counterparts (545.0 prescriptions/1000 inhabitants/year). Hungary had a similar scale of antibacterial exposure across all elderly age subgroups, with different trends in males and females, while Sweden had a stepwise increase in antibiotic exposure by age in both sexes. The seasonal fluctuation was high in Hungary and reached a peak of 80.7 prescriptions/1000 inhabitants/month in January 2017, while even antibiotic use was detected throughout the year in Sweden. The pattern of antibiotic use in the elderly considerably differed between the two countries. Penicillin and beta-lactamase combinations, such as co-amoxiclav, were more frequently used in Hungary than in Sweden (19.08% vs 1.83% of corresponding total ambulatory antibiotic use). Likewise, quinolones were more commonly used in Hungary than in Sweden (34.53% vs. 9.98). The elderly in Sweden were mostly prescribed narrow spectra penicillins (26.71% vs. 0.29% in Hungary). Conclusion: This cross-national comparison revealed important differences in all aspects of antibiotic use in the elderly between the two countries. The identical scale and pattern of antibiotic use cannot be anticipated due to the poorer health status of the Hungarian elderly population. However, the substantial differences indicate some room for improvement in the antibiotic prescription for the Hungarian elderly.

Background Many studies have addressed influenza vaccine uptake in risk-group populations (e.g. the elderly). However, it is also necessary to assess influenza vaccine uptake in the active adult population, since they are considered to be a high-transmitter group. In several countries pharmacists are involved in adult vaccination in order to increase uptake. This study therefore aimed to investigate the determinants of influenza vaccination uptake and examine the willingness to be vaccinated by pharmacists. Methods A cross-sectional study was conducted among Hungarian adults using a self-administered online questionnaire distributed via social media (Facebook). The questionnaire included five domains: demographics, vaccine uptake, factors that motivated or discouraged vaccination, knowledge and willingness of participants to accept pharmacists as influenza vaccine administrators. Descriptive statistics were applied and logistic regression was conducted to assess the possible determinants of vaccination uptake. Results Data from 1631 participants who completed the questionnaires were analysed. Almost 58% of respondents (944/1631) had occupational and/or health risk factors for influenza. Just over one-tenth (12.3%;200/1631) of participants were vaccinated during the 2017/18 influenza season, 15.4% (145/944) of whom had a risk factor for influenza. Approximately half of the participants (47.4%) believed that influenza vaccination can cause flu, and just over half of them (51.6%), were not knowledgeable about the safety of influenza vaccine ingredients. Logistic regression found that age, sex, health risk factor and knowledge on influenza/influenza vaccination were associated with influenza vaccination uptake ( p < 0.05). The most frequently cited reason for having an influenza vaccination was self-protection (95.0%). The most common reason given for refusing the influenza vaccine was that the respondent stated they rarely had an infectious disease (67.7%). The number of participants who were willing to be vaccinated by pharmacists was two-times higher than the number of participants who were actually vaccinated during the 2017/18 influenza season. Conclusion Influenza vaccine uptake in the active adult population is low in Hungary. Public awareness and knowledge about influenza vaccination and influenza disease should be increased. The results also suggest a need to extend the role played by pharmacists in Hungary.

Background Due to their efficacy and tolerability, utilization of proton pump inhibitors (PPI) has significantly increased worldwide. Parallel to the clinical benefits, potential long-term side effects have been observed, which, along with increasing medical expenses and potential drug interactions, justifies the analysis of the trends of utilization. Objective The aim of the present study was to show the level, pattern, and characteristics of PPI use. Methods We assessed the nationwide use of proton pump inhibitors in ambulatory care based on aggregated utilization data from the National Health Insurance database. The annual PPI utilization was expressed as the number of packages and as number of DDDs per 1,000 inhabitants and per year. For 2018, we estimated PPI exposure as the number of packages and as the number of DDDs per user per year. The annual reimbursement costs of proton pump inhibitors were also calculated. Moreover, three patient-level surveys were carried out in non-gastroenterological inpatient hospital departments to reveal characteristics of proton pump inhibitor use, namely dose, duration, and indication. Results The PPI utilisation increased from 5867.8 thousand to 7124.9 thousand packages and from 41.9 to 50.4 DDD per 1,000 inhabitants and per day between 2014 and 2018. Nationwide data showed that 14% of the adult population was exposed to proton pump inhibitors in 2018, while among hospitalized patients, the prevalence of proton pump inhibitor use was between 44.5% and 54.1%. Pantoprazole was the most frequently used active ingredient, both in the nationwide data and in the patient-level surveys. In the patient-level survey in majority of patients (71.5%-80.0%) proton pump inhibitors were prescribed for prophylaxis. Many inpatients (29.4%-36.9%) used 80 mg pantoprazole per day. The average number of PPI packages per user was 6.5 in 2018 in the nationwide data. The duration of PPI therapy was typically between 1 and 5 years in the patient-level surveys and nearly 20% of the inpatients had been taking proton pump inhibitors for more than 5 years. Conclusions Our data suggests that Hungarian patients receive proton pump inhibitors in high doses and for a long time. Use of proton pump inhibitors beyond their recommended indications was also found.

Background Atypical femoral fracture is one of the many complications after the long-term use of bisphosphonates. The American Society for Bone and Mineral Research has officially excluded periprosthetic femoral fractures (PFFs) from the definition of atypical femoral fractures (AFFs). Several case reports found that PFFs can occur with characteristics similar to those of AFFs. The purpose of our study was to evaluate the proportion of atypical fractures among Vancouver type B1 fractures, and to determine the association between the long-term use of bisphosphonates and the occurrence of atypical periprosthetic femoral fractures (APFFs). Methods In this retrospective study, we reviewed 41 patients with Vancouver type B1 periprosthetic fractures between January 1, 2011 and December 31, 2018. We classified them into two groups, namely atypical and typical PFFs, based on the fracture morphology. We noted the proportion of atypical periprosthetic fractures among B1 fractures and identified risk factors. Results Among the 41 PFFs, 5 (13%) fractures were classified as atypical PFF based on the radiological characteristics. The longer duration of bisphosphonate use was probably the only independent risk factor that significantly increases the occurrence of APFF ( p = 0.03, 0.08 (CI 0.008 – 0.16)). There were no significant differences in age, gender, body mass index, comorbidities, corticosteroid use, positioning of the femoral stem, the method of fixation (cemented or cementless) and time lapse from before the primary prosthesis implantation to the PFF in the development of atypical fracture type. Conclusions There seems to be a correlation between the long-term intake of bisphosphonates and the atypical periprosthetic fracture. Atypical femoral fracture can also occur in the periprosthetic form. Trial registration Study number: 22/2019-SZTE, http://www.klinikaikutatas.hu/hu/kutatasetika/jovahagyott-vizsgalatok-koezerdeku-adatai/category/25-jovahagyott-vizsgalatok-kozerdeku-adatai-rkeb-2019.html?download=985:22-2019 .

IntroductionThe importance of rational drug therapy is increasing with the aging of the population. Since one of the main reasons for inappropriate drug prescribing is also the age-blind approach, which results in ageist practices, this narrative literature review focuses on the description of the main barriers related to insufficient individualization of drug regimens associated with such age-blind approaches.MethodologyA narrative literature review using the PubMed, WoS, Embase, and Scopus databases was conducted by the EU COST Action IS1402. Experts in different scientific fields from six countries (the Czech Republic, Spain, Portugal, Hungary, Serbia, and Turkey) worked in four specific areas: (1) underrepresentation of older adults in clinical trials and clinical and ethical consequences; (2) insufficient consideration of age-related changes and geriatric frailty in the evaluation of the therapeutic value of drugs; (3) frequent prescribing of potentially inappropriate medications (PIMs); and (4) frequent underuse of highly beneficial nonpharmacological strategies (e.g., exercise).ResultsOlder patients are underrepresented in clinical trials. Therefore, rigorous observational geriatric research is needed in order to obtain evidence on the real efficacy and safety of frequently used drugs, and e.g. developed geriatric scales and frailty indexes for claims databases should help to stimulate such research. The use of PIMs, unfortunately, is still highly prevalent in Europe: 22.6% in community-dwelling older patients and 49.0% in institutionalized older adults. Specific tests to detect the majority of age-related pharmacological changes are usually not available in everyday clinical practice, which limits the estimation of drug risks and possibilities to individualize drug therapy in geriatric patients before drug prescription. Moreover, the role of somenonpharmacological strategies is highly underestimated in older adultsin contrast to frequent use of polypharmacy. Among nonpharmacological strategies, particularly physical exercise was highly effective in reducing functional decline, frailty, and the risk of falls in the majority of clinicalstudies.ConclusionSeveral regulatory and clinical barriers contribute to insufficient knowledge on the therapeutic value of drugs in older patients, age-blind approach, and inappropriate prescribing. New clinical and observational research is needed, including data on comprehensive geriatric assessment and frailty, to document the real efficacy and safety of frequently used medications.

BACKGROUND:The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. METHODS:Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. RESULTS:PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). CONCLUSIONS:The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.

Objective In intensive care units numerous drugs have to be infused simultaneously, resulting inline incompatibility. Propofol is formulated as a lipid emulsion and it is well known that electrolytes can affect the stability of an emulsion system. Our goal was to evaluate and to compare the physical compatibility of three commercial propofol lipid emulsions of different manufacturers, mixing them with the most commonly used crystalloids in intensive care units. Methods Simulated Y-site administration was accomplished by mixing the 2% MCT/LCT propofol emulsions with the commonly used crystalloids in the intensive care unit in a 1:1 ratio in a polypropylene syringe. The aliquot samples were evaluated immediately and at 15, 30, 60 and 120 min after preparation by visual observation, pH and droplet size measurement. Results There was no emulsion breakdown or any visible change during the study period. Mixing the propofols with crystalloids, 10% magnesium sulphate or 10% potassium chloride there was no significant change in the droplet size compared with the original propofol emulsions. A slight alteration in droplet size was noticed in a few of the propofol samples, when magnesium, potassium or both were the secondary additives to the crystalloids, but this is not considered clinically relevant. Conclusion The physical properties of emulsions are determined by component, therefore the compatibility data in literature has to be evaluated prudently. All three commercially available MCT/LCT propofol emulsions are considered physically compatible with the tested crystalloids.

Background Geriatric falls are leading causes of hospital trauma admissions and injury-related deaths. Medication use is a crucial element among extrinsic risk factors for falls. To reduce fall risk and the prevalence of adverse drug reactions, potentially inappropriate medication (PIM) lists are widely used. Objective Our aim was to investigate the possible predictors of geriatric falls annualized over a 5-year-long period, as well as to evaluate the medication use of nursing home residents. Setting Nursing home residents were recruited from the same institution between 2010 and 2015 in Szeged, Hungary. Method A retrospective epidemiological study was performed. Patient data were analysed for the first 12 months of residency. Chi-squared test and Fisher's-test were applied to compare the categorical variables, Student's t test to compare the continuous variables between groups. Binary logistic regression analysis was carried out to determine the association of falls with other variables found significant in univariate analysis. Microsoft Excel, IBM SPSS Statistics (version 23) and R (3.2.2) programs were used for data analysis. Main outcome measure Falls affected by age, gender, number of chronic medications, polypharmacy, PIM meds. Results A total of 197 nursing home residents were included, 150 (76.2%) women and 47 (23.8%) men, 55 fallers (annual fall prevalence rate was 27.9%) and 142 non-fallers. Gender was not a predisposing factor for falls (prevalence in males: 23.4 vs 29.3% in females, p > 0.05). Fallers were older (mean years ± SD; 84.0 ± 7.0) than non-fallers (80.1 ± 9.3, p < 0.01). The age ≥80 years was a significant risk factor for falls (p < 0.001). The number of chronic medications was higher in male fallers (12.4 ± 4.0) than in non-fallers (6.9 ± 4.2, p < 0.001). Polypharmacy (taking four or more chronic medications) was a significant risk factor of falls (p < 0.01). Those PIMs carrying fall risk were taken by 70.9% of fallers and 75.3% of non-fallers (p > 0.05). Taking pantoprazole, vinpocetine or trimetazidine was a significant risk factor for falls. Conclusion Older age, polypharmacy and the independent use of pantoprazole, vinpocetine, and trimetazidine were found to be major risk factors for falls. Further real-life epidemiological studies are necessary to confirm the role of particular active agents, and to help professionals prescribe, evaluate and review geriatric medication use.