Assessment of potentially inappropriate medication use among geriatric outpatients in the Slovak Republic.

BACKGROUND: Potentially inappropriate medication (PIM) use is a highly prevalent problem among older people, making it challenging to improve patient safety. The aim of this study was to assess the use of PIMs among geriatric outpatients (OUTs) in the Slovak Republic according to the EU(7) PIM list and to identify the differences in PIM prescriptions among general practitioners (GPs), internists (INTs) and geriatricians (GERs). METHODS: In total, 449 patients (65 years and older) from 4 medical centres who were in the care of GPs (32.5%), INTs (22.7%) or GERs (44.8%) were included in this retrospective analysis. Data were collected from 1.12.2019-31.3.2020. PIMs were identified according to the EU(7) PIM list from patients' records. PIM prescriptions by GPs, INTs and GERs were assessed. All obtained data were statistically analysed. RESULTS: Polypharmacy (68.8% of patients), and PIM use (73% of patients) were observed. The mean number of all prescribed drugs was 6.7 ± 0.2 drugs per day/patient. The mean number of prescribed PIMs was 1.7 ± 0.1 PIMs per day/patient. Drugs from Anatomical Therapeutic Chemical (ATC) classes C, N and A accounted for the greatest number of PIMs. Significantly higher numbers of prescribed drugs as well as PIMs were prescribed by GPs than INTs or GERs. There were 4.2 times higher odds of being prescribed PIMs by GPs than by GERs (p < 0.001). CONCLUSIONS: Polypharmacy and overprescription of PIMs were identified among geriatric patients in our study. We found a positive relationship between the number of prescribed drugs and PIMs. The lowest odds of being prescribed PIMs were observed among those who were in the care of a geriatrician. The absence of geriatricians and lack of information about PIMs among general practitioners leads to high rates of polypharmacy and overuse of potentially inappropriate medications in geriatric patients in the Slovak Republic.

Availability and Accessibility of Orphan Medicinal Products to Patients in Slovakia in the Years 2010-2019.

Objective: Information about the access of Slovak patients to orphan medicinal products (OMPs) in the literature is rather scarce. The main aim of the study was to analyze the accessibility and availability of OMPs to Slovak patients in the years 2010-2019. Methods: The analyzed OMPs were strictly defined according to the European definition. The date of marketing authorization together with its first appearance in the positive drug list was used to count the time to reach the national market. The data from the National Health Information Centre, the Ministry of Health, and health insurance companies were used as data sources of drug usage, expenditure, consumption, reimbursement of OMPs, as well as the total number of treated patients. Results: Out of the 167 OMPs on the European market, we identified 52% (87) OMPs which had any kind of costs recorded in Slovakia. Out of them, 62% (54) OMPs were directly present on the positive drug list. The remaining 33 OMPs were available on exception. The trend in accessibility and availability of OMPs in Slovakia between the years 2010 and 2019 was decreasing (57% OMPs in 2010 vs. 47% OMPs in 2019). The average time for an orphan medicinal product to reach the Slovak market was almost 4 years, 43.5 months [6-202 months]. Together, 10.4% (8 815 patients) out of the theoretical patients' estimation according to the prevalence in the orphan designation were treated with OMPs available in Slovakia. Conclusion: Presented data clearly show insufficient accessibility and availability of OMPs in Slovakia. Importance of clearly defined criteria for OMPs supporting patients and healthcare professionals' involvement in the final decision together with other measures such as social impact, improvement of patients' quality of life, society wide meaning, or no alternative treatment in the final decision is crucial for transparent and sustainable access to OMPs and innovative treatments in Slovakia.

The analysis of the use of potentially inappropriate medications in elderly in the Slovak Republic.

Background The prevalence of potentially inappropriate medications (PIM) using explicit criteria has been well documented in European countries, however, there is a lack of evidence in the Slovak Republic. There are no specific guidelines and there is a lack of geriatricians in Slovakia. Higher use of PIM leads to greater healthcare services use as well as increases healthcare costs. Objective The aim of this study was to perform an evaluation of the availability and the actual use of PIM by geriatric patients in the nursing homes in Slovakia. Setting Together 459 residents ≥ 65 years living in nursing homes in the Slovak Republic were included for analysis of their drug therapy. Methods Retrospective analysis of medical records of patients' therapy for evaluation of PIM use. Identification of PIM was based on the Renom-Guiteras EU7 PIM list published in 2015. Main outcome measure Potentially inappropriate medications use. The presence of polypharmacy in patients. Results Inappropriate drug use according to EU7 PIM list was identified in 90.60% (416) patients. The mean number of PIM was 2.34 ± 0.07 PIM/patient/day. Polypharmacy (use of ≥ 5 drugs by patient daily) was found in 83% of all patients. The mean number of prescribed drugs was 8.32 ± 0.17 drugs/patient/day. Out of all 282 PIM listed in EU7 PIM list, there are 150 (53.19%) available on the Slovak market and 86 (30.50%) were used in patients. Patients using at least one PIM took two times more drugs compared to patients without PIM (8.77 ± 0.17 vs. 3.98 ± 0.39 drugs/patient/day, p < 0.001). The most common PIM were PPI (36% of patients), piracetam (17.2%) and alprazolam (16.80%). Conclusions The risk of PIM was almost 9.5 times higher if polypharmacy was present in geriatric patients (OR 9.51, 95% CI, 4.86 - 18.61, p < 0.001). There was a strong, positive correlation (ρ = 0.65) between the number of drugs and the number of PIM (p < 0.01). There was neither association between age/gender of patient and polypharmacy; nor age/gender of patient and presence of PIM. The lack of geriatricians and national guidelines for inappropriate prescribing results in alarmingly high use of PIM in the Slovak Republic.

Caustic Ingestion in the Elderly: Influence of Age on Clinical Outcome.

Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure, substance ingested, severity of mucosal injury, complications, and mortality. Caustic substance exposures reported to the National Toxicological Information Centre in Slovakia during 1998-2015 were reviewed retrospectively. The patients were divided into two groups: the non-elderly (<60 years) and elderly adults (≥60 years). The mortality rate in the elderly was significantly higher (elderly 23.0% vs. non-elderly 11.3%; p = 0.041). The risk of fatal outcome in the elderly was increased by acid ingestion (OR = 7.822; p = 0.002), particularly hydrochloric acid (OR = 5.714, p = 0.006). The incidence of respiratory complications was almost two times higher in the elderly was 31.1% vs. 17.4% for the non-elderly (p = 0.037). Respiratory complications significantly correlated with an increased mortality rate (p = 0.001) in the elderly whereas there was no association between GI complications and mortality in the elderly (p = 0.480). Elderly patients with respiratory complications had the poorest clinical outcomes. The highest risk of complications and fatalities was observed in patients after hydrochloric acid ingestion.

The Effects of Pycnogenol® as Add-on Drug to Metformin Therapy in Diabetic Rats.

The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy. Copyright © 2016 John Wiley & Sons, Ltd.

Use of biomarkers in the context of orphan medicines designation in the European Union.

The use of biomarkers within the procedures of the Committee of Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) is discussed herein. The applications for Orphan Medicinal Product designation in the EU are evaluated at two stages. At the time of orphan designation application, the file undergoes an assessment to establish whether the proposed condition is a distinct and serious condition affecting not more than 5 in 10,000 people in the EU, and whether the product is plausible as a therapy for that condition. In cases where therapies already exist, the significant benefit of the candidate product over existing therapies is also evaluated. The orphan criteria are reassessed at the time of marketing authorisation, so that marketing exclusivity for the product in the orphan medical condition can be granted. Within this context, biomarkers have been used in submissions in order to define an orphan condition and to justify that the criteria for orphan designation are met. The current work discusses specific examples from the experience of the COMP, where biomarkers have played a decisive role. Importantly, it identifies the proposal of sub-sets of non-rare conditions based on biomarkers as a challenging issue in the evaluation of applications. In particular two specific requirements for the candidate orphan medicines in relation to the biomarker-based subsets are highlighted: the "plausible link to the condition" and the "exclusion of effects outside the subset".

MEG3: a novel long noncoding potentially tumour-suppressing RNA in meningiomas.

Meningiomas represent one of the most common types of primary intracranial tumours. However, the specific molecular mechanisms underlying their pathogenesis remain uncertain. Loss of chromosomes 22q, 1p, and 14q have been implicated in most meningiomas. Inactivation of the NF2 gene at 22q12 has been identified as an early event in their pathogenesis, whereas abnormalities of chromosome 14 have been reported in higher-grade as well as recurrent tumours. It has long been supposed that chromosome 14q32 contains a tumour suppressor gene. However, the identity of the potential 14q32 tumour suppressor remained elusive until the Maternally Expressed Gene 3 (MEG3) was recently suggested as an ideal candidate. MEG3 is an imprinted gene located at 14q32 that encodes a non-coding RNA (ncRNA). In meningiomas, loss of MEG3 expression, its genomic DNA deletion and degree of promoter methylation have been found to be associated with aggressive tumour growth. These findings indicate that MEG3 may have a significant role as a novel long noncoding RNA tumour suppressor in meningiomas.

Characteristics of elderly patients who consider over-the-counter medications as safe.

BACKGROUND: There is a lack of studies evaluating the factors which influence the perception of safety of over-the-counter (OTC) medications by elderly patients. OBJECTIVE: The aim of our questionnaire survey was to evaluate the perception of the risk of OTC medications by elderly patients and to identify patient-associated characteristics which determine elderly persons who consider OTC medications as safe. SETTING: 25 community pharmacies in different regions of the Slovak Republic. METHODS: A 54-items questionnaire was provided to patients aged ≥65 years who were purchasing at least one OTC medication during the period from May 2010 to November 2010. The questions elicited information on (a) self-assessment of health status; (b) basic characteristics of OTC medications use (e.g. frequency, duration); (c) patients' knowledge on OTC medications; (d) participants' perception of the risk of OTC medications; (e) the list of OTC and prescription-only medications taken; and (f) sociodemographic characteristics of respondents. RESULTS: Of the 793 questionnaires distributed, 519 were finally included in the statistical analysis (response rate of 65.4 %). Women were prevailing in the analysed group (n = 361; 69.6 %). The average age of participants was 72.2 ± 5.6 years. Majority (n = 392, 75.5 %) of the respondents considered OTC medications as safe. Multivariate analysis (binary logistic regression) revealed that elderly patients who considered OTC medications as safe were characterised by use of OTC medications every day (OR = 2.09), preferring a wide range of such drugs in pharmacies (OR = 2.86), considering such medications as effective (OR = 10.33), obtaining information on OTC drugs from pharmacists (OR = 1.91) and willingness to possibly purchase OTC medications outside pharmacies (OR = 3.35). On the other hand, allergic conditions as a reason for purchasing OTC medications (OR = 0.23), recommendation of a physician regarding the choice of OTC medications (OR = 0.51) and considering concurrent use of several medications as a factor increasing the risk of adverse drug reactions (OR = 0.62) emerged as important factors that decreased the probability of elderly patients considering OTC medications as safe. CONCLUSIONS: The survey identified various factors that influenced the perceptions of the safety of OTC medications by the elderly and indicated that pharmacists represent the most trusted source of information about OTC medications.

European regulation on orphan medicinal products: 10 years of experience and future perspectives.

In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments.