Survey of Potential Drug Interactions, Use of Non-Medical Health Products, and Immunization Status among Patients Receiving Targeted Therapies.

In recent years, several changes have occurred in the management of chronic immunological conditions with the emerging use of targeted therapies. This two-phase cross-sectional study was conducted through structured in-person interviews in 2018-2019 and 2022. Additional data sources included ambulatory medical records and the itemized reimbursement reporting interface of the National Health Insurance Fund. Drug interactions were analyzed using the UpToDate Lexicomp, Medscape drug interaction checker, and Drugs.com databases. The chi-square test was used, and odds ratios (ORs) were calculated. In total, 185 patients participated. In 53% of patients (n = 53), a serious drug-drug interaction (DDI) was identified (mean number: 1.07 ± 1.43, 0-7), whereas this value was 38% (n = 38) for potential drug-supplement interactions (mean number: 0.58 ± 0.85, 0-3) and 47% (n = 47) for potential targeted drug interactions (0.72 ± 0.97, 0-5) in 2018. In 2022, 78% of patients (n = 66) were identified as having a serious DDI (mean number: 2.27 ± 2.69, 0-19), 66% (n = 56) had a potential drug-supplement interaction (mean number: 2.33 ± 2.69, 0-13), and 79% (n = 67) had a potential targeted drug interactions (1.35 ± 1.04, 0-5). Older age (>60 years; OR: 2.062), female sex (OR: 3.387), and polypharmacy (OR: 5.276) were identified as the main risk factors. Screening methods and drug interaction databases do not keep pace with the emergence of new therapeutics.

Leveraging code-free deep learning for pill recognition in clinical settings: A multicenter, real-world study of performance across multiple platforms.

BACKGROUND: Preventable patient harm, particularly medication errors, represent significant challenges in healthcare settings. Dispensing the wrong medication is often associated with mix-up of lookalike and soundalike drugs in high workload environments. Replacing manual dispensing with automated unit dose and medication dispensing systems to reduce medication errors is not always feasible in clinical facilities experiencing high patient turn-around or frequent dose changes. Artificial intelligence (AI) based pill recognition tools and smartphone applications could potentially aid healthcare workers in identifying pills in situations where more advanced dispensing systems are not implemented. OBJECTIVE: Most of the published research on pill recognition focuses on theoretical aspects of model development using traditional coding and deep learning methods. The use of code-free deep learning (CFDL) as a practical alternative for accessible model development, and implementation of such models in tools intended to aid decision making in clinical settings, remains largely unexplored. In this study, we sought to address this gap in existing literature by investigating whether CFDL is a viable approach for developing pill recognition models using a custom dataset, followed by a thorough evaluation of the model across various deployment scenarios, and in multicenter clinical settings. Furthermore, we aimed to highlight challenges and propose solutions to achieve optimal performance and real-world applicability of pill recognition models, including when deployed on smartphone applications. METHODS: A pill recognition model was developed utilizing Microsoft Azure Custom Vision platform and a large custom training dataset of 26,880 images captured from the top 30 most dispensed solid oral dosage forms (SODFs) at the three participating hospitals. A comprehensive internal and external testing strategy was devised, model's performance was investigated through the online API, and offline using exported TensorFlow Lite model running on a Windows PC and on Android, using a tailor-made testing smartphone application. Additionally, model's calibration, degree of reliance on color features and device dependency was thoroughly evaluated. Real-world performance was assessed using images captured by hospital pharmacists at three participating clinical centers. RESULTS: The pill recognition model showed high performance in Microsoft Azure Custom Vision platform with 98.7 % precision, 95.1 % recall, and 98.2 % mean average precision (mAP), with thresholds set to 50 %. During internal testing utilizing the online API, the model reached 93.7 % precision, 88.96 % recall, 90.81 % F1-score and 87.35 % mAP. Testing the offline TensorFlow Lite model on Windows PC showed a slight performance reduction, with 91.16 % precision, 83.82 % recall, 86.18 % F1-score and 82.55 % mAP. Performance of the model running offline on the Android application was further reduced to 86.50 % precision, 75.00 % recall, 77.83 % F1-score and 69.24 % mAP. During external clinical testing through the online API an overall precision of 83.10 %, recall of 71.39 %, and F1-score of 75.76 % was achieved. CONCLUSION: Our study demonstrates that using a CFDL approach is a feasible and cost-effective method for developing AI-based pill recognition systems. Despite the limitations encountered, our model performed well, particularly when accessed through the online API. The use of CFDL facilitates interdisciplinary collaboration, resulting in human-centered AI models with enhanced real-world applicability. We suggest that rather than striving to build a universally applicable pill recognition system, models should be tailored to the medications in a regional formulary or needs of a specific clinic, which can in turn lead to improved performance in real-world deployment in these locations. Parallel to focusing on model development, it is crucial to employ a human centered approach by training the end users on how to properly interact with the AI based system to maximize benefits. Future research is needed on refining pill recognition models for broader adaptability. This includes investigating image pre-processing and optimization techniques to enhance offline performance and operation on handheld devices. Moreover, future studies should explore methods to overcome limitations of CFDL development to enhance the robustness of models and reduce overfitting. Collaborative efforts between researchers in this domain and sharing of best practices are vital to improve pill recognition systems, ultimately enhancing patient safety and healthcare outcomes.

Declaration of common standards for the preregistration of animal research-speeding up the scientific progress.

Preregistration of studies is a recognized tool in clinical research to improve the quality and reporting of all gained results. In preclinical research, preregistration could boost the translation of published results into clinical breakthroughs. When studies rely on animal testing or form the basis of clinical trials, maximizing the validity and reliability of research outcomes becomes in addition an ethical obligation. Nevertheless, the implementation of preregistration in animal research is still slow. However, research institutions, funders, and publishers start valuing preregistration, and thereby level the way for its broader acceptance in the future. A total of 3 public registries, the OSF registry, preclinicaltrials.eu, and animalstudyregistry.org already encourage the preregistration of research involving animals. Here, they jointly declare common standards to make preregistration a valuable tool for better science. Registries should meet the following criteria: public accessibility, transparency in their financial sources, tracking of changes, and warranty and sustainability of data. Furthermore, registration templates should cover a minimum set of mandatory information and studies have to be uniquely identifiable. Finally, preregistered studies should be linked to any published outcome. To ensure that preregistration becomes a powerful instrument, publishers, funders, and institutions should refer to registries that fulfill these minimum standards.

Follow-Up of Blood Pressure, Arterial Stiffness, and GFR in Pediatric Kidney Transplant Recipients.

Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function. Patients and Methods: 52 RTx patients (22 males) were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0-4.7] (T1) and 9.3[6.3-11.8] years (T2) after transplantation (median [range]). Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2. Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR.

Distance measurement for pulse wave velocity estimation in pediatric age: Comparison with intra-arterial path length.

BACKGROUND AND AIMS: Central pulse wave velocity (PWV) is a marker of arterial stiffness and is calculated by dividing the pulse wave travel distance by the transit time. However, there is no consensus as to the ideal distance measurement in children. The aim of our study was to identify the more reliable method to assess the distance measurement in the pediatric age. METHODS: Carotid-femoral PWV was measured by applanation tonometry in 988 healthy children aged 6.5-19.9 years. Two different surface distances were assessed: the subtraction method, representing the distance from the suprasternal notch to the femoral artery minus the distance from the carotid artery to the suprasternal notch, and the direct method, consisting of 80% of the distance from the carotid artery to the femoral artery. Both these methods were compared with the actual path length determined by magnetic resonance imaging (MRI) in 31 children. RESULTS: Subtraction and direct methods were significantly correlated in patients aged <14 years and the corresponding PWV values showed a good agreement. In children aged ≥14 years, a significant difference between the two methods was found: subtraction - direct distance = -45 ± 28 mm, with a significant difference in the resulting PWV values = -0.57 ± 0.35 m/s (p < 0.0001). This result was confirmed by MRI, showing a 10% overestimation in distance measurement by the direct method in subjects aged ≥14 years, resulting in a significantly higher PWV. CONCLUSIONS: These data suggest a greater reliability of the subtractive method of distance measurement compared to the direct method in children.

Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1.

Electronic pacemakers still face major shortcomings that are largely intrinsic to their hardware-based design. Radical improvements can potentially be generated by gene or cell therapy-based biological pacemakers. Our previous work identified adenoviral gene transfer of Hcn2 and SkM1, encoding a "funny current" and skeletal fast sodium current, respectively, as a potent combination to induce short-term biological pacing in dogs with atrioventricular block. To achieve long-term biological pacemaker activity, alternative delivery platforms need to be explored and optimized. The aim of the present study was therefore to investigate the functional delivery of Hcn2/SkM1 via human cardiomyocyte progenitor cells (CPCs). Nucleofection of Hcn2 and SkM1 in CPCs was optimized and gene transfer was determined for Hcn2 and SkM1 in vitro. The modified CPCs were analyzed using patch-clamp for validation and characterization of functional transgene expression. In addition, biophysical properties of Hcn2 and SkM1 were further investigated in lentivirally transduced CPCs by patch-clamp analysis. To compare both modification methods in vivo, CPCs were nucleofected or lentivirally transduced with GFP and injected in the left ventricle of male NOD-SCID mice. After 1 week, hearts were collected and analyzed for GFP expression and cell engraftment. Subsequent functional studies were carried out by computational modeling. Both nucleofection and lentiviral transduction of CPCs resulted in functional gene transfer of Hcn2 and SkM1 channels. However, lentiviral transduction was more efficient than nucleofection-mediated gene transfer and the virally transduced cells survived better in vivo. These data support future use of lentiviral transduction over nucleofection, concerning CPC-based cardiac gene delivery. Detailed patch-clamp studies revealed Hcn2 and Skm1 current kinetics within the range of previously reported values of other cell systems. Finally, computational modeling indicated that CPC-mediated delivery of Hcn2/SkM1 can generate stable pacemaker function in human ventricular myocytes. These modeling studies further illustrated that SkM1 plays an essential role in the final stage of diastolic depolarization, thereby enhancing biological pacemaker functioning delivered by Hcn2. Altogether these studies support further development of CPC-mediated delivery of Hcn2/SkM1 and functional testing in bradycardia models.

Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high-performance liquid chromatography.

Administration of the increasingly popular dietary supplements containing quercetin may interfere with drug therapy. We intended to evaluate the online availability and quercetin content of the high-dose mono-component quercetin products and to review the potential use of quercetin products and their interactions with drugs. We monitored the online access to quercetin-containing dietary supplements, collected the relevant information from the websites, procured selected products from the vendors, and subjected them to substance analysis. The quercetin content was quantified by an HPLC-UV method. Twenty-five websites offered mono-component quercetin products, and nine products were procured. The quercetin content of eight products differed only ±10% from the nominal dose, whereas one product contained almost 30% more quercetin. Misleading indications such as antitumor and cardiovascular effects were often found on the sellers' websites. Quercetin-containing dietary supplements are available online with misleading indications. The recommended daily doses are often high (occasionally over 1,000 mg), which may induce clinically relevant interactions with medications. Because high-quercetin content of dietary supplements was confirmed, health care professionals should be aware of the unregulated internet market of dietary supplements and should consider the interactions of these substances with drugs.

Countrywide prevalence of critical drug interactions in Hungarian outpatients: a retrospective analysis of pharmacy dispensing data.

BACKGROUND: Drug-drug interactions (DDIs) present a significant source of adverse drug reactions. Despite being one of the commonly cited risks to patient safety, prevention of DDIs still poses a challenge to healthcare systems. The prevalence of DDIs can be used as a quality indicator for the safety of prescribing. With the analysis of drug utilization databases, real-world data on critical DDIs can be obtained. The aim of this study was to establish a list of critical DDIs and estimate their prevalence in the Hungarian outpatient population. METHODS: Since there is no conclusive and generally accepted repository of high-risk DDIs, a systematic search of the literature for consensus-based lists was performed. Based on these results and their analysis with 5 interaction compendia, we propose a simple methodology to identify critical combinations. Present study focused on DDIs which are (1) of high clinical importance thus being most likely to cause significant harm if not detected, (2) well-supported by available evidence and (3) affect drugs which are routinely dispensed in the community pharmacy setting. A retrospective analysis of prescriptions filled between 2013 and 2016 was performed. The source of drug utilization data was the IQVIA's national prescription fill database. The number of interacting drug pairs dispensed at the same time to the same patient was established. RESULTS: After excluding drugs with low dispensing rates, the analysis covered 39 DDIs. The distribution of risk categories of the analysed DDIs was inconsistent among different drug interaction compendia. The total number of prescriptions filled varied between 173924449 and 176368468 per year. The prevalence of the selected potential DDIs ranged from 0.00 to 355.89 per 100000 prescriptions per year. There was significant variation between how the number of cases had changed for each DDI throughout the study period, no general tendency could have been described. CONCLUSIONS: There were 1.8 million cases of co-dispensing each year, where prescribers' and community pharmacists' role in recognizing and managing potentially serious interactions was or would have been critical. The method presented to identify high-risk DDIs can serve as a starting point for the much-needed improvement of routine interaction screening.

Cardiomyocyte Progenitor Cells as a Functional Gene Delivery Vehicle for Long-Term Biological Pacing.

Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (-20 pA/pF at -140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.

Human Cardiomyocyte Progenitor Cells in Co-culture with Rat Cardiomyocytes Form a Pro-arrhythmic Substrate: Evidence for Two Different Arrhythmogenic Mechanisms.

Background: Cardiomyocyte progenitor cells (CMPCs) are a promising cell source for regenerative cell therapy to improve cardiac function after myocardial infarction. However, it is unknown whether undifferentiated CMPCs have arrhythmogenic risks. We investigate whether undifferentiated, regionally applied, human fetal CMPCs form a pro-arrhythmic substrate in co-culture with neonatal rat ventricular myocytes (NRVMs). Method: Unipolar extracellular electrograms, derived from micro-electrode arrays (8 × 8 electrodes) containing monolayers of NRVMs (control), or co-cultures of NRVMs and locally seeded CMPCs were used to determine conduction velocity and the incidence of tachy-arrhythmias. Micro-electrodes were used to record action potentials. Conditioned medium (Cme) of CMPCs was used to distinguish between coupling or paracrine effects. Results: Co-cultures demonstrated conduction slowing (5.6 ± 0.3 cm/s, n = 50) compared to control monolayers (13.4 ± 0.4 cm/s, n = 26) and monolayers subjected to Cme (13.7 ± 0.6 cm/s, n = 11, all p < 0.001). Furthermore, co-cultures had a more depolarized resting membrane than control monolayers (-47.3 ± 17.4 vs. -64.8 ± 7.7 mV, p < 0.001) and monolayers subjected to Cme (-64.4 ± 8.1 mV, p < 0.001). Upstroke velocity was significantly decreased in co-cultures and action potential duration was prolonged. The CMPC region was characterized by local ST-elevation in the recorded electrograms. The spontaneous rhythm was faster and tachy-arrhythmias occurred more often in co-cultured monolayers than in control monolayers (42.0 vs. 5.4%, p < 0.001). Conclusion: CMPCs form a pro-arrhythmic substrate when co-cultured with neonatal cardiomyocytes. Electrical coupling between both cell types leads to current flow between a, slowly conducting, depolarized and the normal region leading to local ST-elevations and the occurrence of tachy-arrhythmias originating from the non-depolarized zone.

Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies.

RATIONALE: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date, there has been no systematic overview and meta-analysis of studies using CSC therapy for MI. OBJECTIVE: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. METHODS AND RESULTS: A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSC-treated animals was 10.7% (95% confidence interval 9.4-12.1; P<0.001) improvement in ejection fraction compared with placebo controls. Interestingly, CSC therapy had a greater effect in small animals compared with large animals (P<0.001). Meta-regression indicated that cell type was a significant predictor for ejection fraction improvement in small animals. Minor publication bias was observed in small animal studies. CONCLUSIONS: CSC treatment resulted in significant improvement of ejection fraction in preclinical animal models of MI compared with placebo. There was a reduction in the magnitude of effect in large compared with small animal models. Although different CSC types have overlapping culture characteristics, we observed a significant difference in their effect in post-MI animal studies.

Genome-wide analysis reveals NRP1 as a direct HIF1α-E2F7 target in the regulation of motorneuron guidance in vivo.

In this study, we explored the existence of a transcriptional network co-regulated by E2F7 and HIF1α, as we show that expression of E2F7, like HIF1α, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1α. Our genome-wide analysis uncovers a transcriptional network that is directly controlled by HIF1α and E2F7, and demonstrates both stimulatory and repressive functions of the HIF1α -E2F7 complex. Among this network we reveal Neuropilin 1 (NRP1) as a HIF1α-E2F7 repressed gene. By performing in vitro and in vivo reporter assays we demonstrate that the HIF1α-E2F7 mediated NRP1 repression depends on a 41 base pairs 'E2F-binding site hub', providing a molecular mechanism for a previously unanticipated role for HIF1α in transcriptional repression. To explore the biological significance of this regulation we performed in situ hybridizations and observed enhanced nrp1a expression in spinal motorneurons (MN) of zebrafish embryos, upon morpholino-inhibition of e2f7/8 or hif1α Consistent with the chemo-repellent role of nrp1a, morpholino-inhibition of e2f7/8 or hif1α caused MN truncations, which was rescued in TALEN-induced nrp1a(hu10012) mutants, and phenocopied in e2f7/8 mutant zebrafish. Therefore, we conclude that repression of NRP1 by the HIF1α-E2F7 complex regulates MN axon guidance in vivo.

Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development.

The autonomic nervous system (cANS) is essential for proper heart function, and complications such as heart failure, arrhythmias and even sudden cardiac death are associated with an altered cANS function. A changed innervation state may underlie (part of) the atrial and ventricular arrhythmias observed after myocardial infarction. In other cardiac diseases, such as congenital heart disease, autonomic dysfunction may be related to disease outcome. This is also the case after heart transplantation, when the heart is denervated. Interest in the origin of the autonomic nerve system has renewed since the role of autonomic function in disease progression was recognized, and some plasticity in autonomic regeneration is evident. As with many pathological processes, autonomic dysfunction based on pathological innervation may be a partial recapitulation of the early development of innervation. As such, insight into the development of cardiac innervation and an understanding of the cellular background contributing to cardiac innervation during different phases of development is required. This review describes the development of the cANS and focuses on the cellular contributions, either directly by delivering cells or indirectly by secretion of necessary factors or cell-derivatives.

The epicardium as modulator of the cardiac autonomic response during early development.

The cardiac autonomic nervous system (cANS) modulates heart rate, contraction force and conduction velocity. The embryonic chicken heart already responds to epinephrine prior to establishment of the cANS. The aim of this study was to define the regions of the heart that might participate in modulating the early autonomic response to epinephrine. Immunofluorescence analysis reveals expression of neural markers tubulin beta-3 chain and neural cell adhesion molecule in the epicardium during early development. In addition, expression of the ß2 adrenergic receptor, the receptor for epinephrine, was found in the epicardium. Ex-ovo micro-electrode recordings in hearts with inhibition of epicardial outgrowth showed a significantly reduced response of the heart rate to epinephrine compared to control hearts. This study suggests a role for the epicardium as autonomic modulator during early cardiac development.

[Comprehensive evaluation of drug interaction screening programs: discrepancies and concordances]. / Gyógyszerkölcsönhatások kiszurésére szolgáló adatbázisok értékelése: ellentmondások és egyezoségek.

INTRODUCTION: Recognition of potentially harmful drug interactions is one of the duties of healthcare. However, solutions involving databases are fraught with contradictions due to the lack of standardized principles and data. AIM: The aims of the authors were to perform a comparative evaluation of Hungarian and international databases and to explore ambiguities and contradictions in order to develop more standardized criteria for screening interactions. METHOD: Four Hungarian and two English-language websites and software, and the summaries of product characteristics were compared. The authors analyzed 40 drug-drug and 8 drug-supplement interactions and looked at 8 cases, which represent 28 pairs of interacting substances. RESULTS: The databases warn about most interactions, but these warnings were rarely helpful in preventing undesired consequences. The authors found discrepancies between the databases in 70% of interactions. When looking at different products with the same active ingredients, discrepancies cropped up in 0-66.7% of the cases. Up to 80% of searches for supplementary product interactions did not produce satisfactory results. CONCLUSIONS: In the present situation mapping these ambiguities and creating a standardized classification system would be advantageous.

Identification and evaluation of drug-supplement interactions in Hungarian hospital patients.

BACKGROUND: The increasing number of patients taking supplementary products together with prescribed medicines has become a new challenge for health care systems. These products may influence therapy outcomes by inducing unwanted effects. Particularly concerning is the potential for harmful interactions between prescribed medicines and supplementary products. OBJECTIVE: The aims of the study were to evaluate supplement use, to identify and analyse potential interactions, and to assess the efficiency of computerised interaction screening. SETTING: Participants of the study were inpatients and outpatients of a Hungarian university hospital. METHOD: A cross-sectional point-of-care survey of 200 patients was carried out. Data was collected through personal interviews and a review of the medical records. Drug-drug, drug-supplement and supplement-supplement interactions were analysed with three interaction databases (Lexi-Interact Online, Medscape Drug Interaction Checker and Mediris). MAIN OUTCOME MEASURE: Prevalence of supplementary product use, number of medicines and supplementary products per patient, procurement sources of products, number of potentially severe interactions. RESULTS: There was a marked difference between data obtained from patient interviews and the medical records. 85.5 % of the surveyed patients took supplementary products during the 2 weeks prior to the interview. The average number of prescribed medicines and supplementary products were 7.8 and 2.5, respectively. Women were more likely to take supplements than men. There was no significant difference in supplement use between patients under or over 60 years, between inpatients and outpatients and among patients in various wards. 39.4 % of supplementary products were purchased outside a regulated pharmacy environment. Potentially severe drug-supplement interactions were detected with 45.2 % of supplement users; however the majority of interactions were not included in one or the other of the three databases. In addition to that the risk ratings of the same interactions varied greatly between databases. CONCLUSION: A significant number of patients are exposed to potential drug interactions with supplementary products; however interagreement among interaction databases is poor. Our data suggest that a full medication history should specifically address the intake of supplements.

Composition and antipseudomonal effect of essential oils isolated from different lavender species.

The aims of our research include the phytochemical characterization of the essential oils extracted from different lavender species (Lavandula vera L., L. intermedia L., L. pyrenaica DC., and L. stoechas subsp. stoechas) that are important from therapeutic and economic aspects, as well as the optimization of the tube dilution method for microbiological investigation of the effect of essential oils on the selected Pseudomonas strain. The chemical and percentage compositions of the essential oils were analysed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component of the essential oils in the majority of lavender species was linalool, while L-fencone was identified in the largest amount in L. stoechas subsp. stoechas. Tube dilution is one of the most frequently used methods for microbiological investigation. Its advantages are that it is easy to perform and provides information about minimum bactericidal concentration (MBC). Because of the lipophilic character of essential oils, the tube dilution method should be optimized for the detection of antibacterial activity of these plant extracts, and, therefore, emulsions containing 0.2% polysorbate 80 were prepared from the samples. In each of the eight investigated essential oils an inhibitory effect was detected, and MBC values were in the range 12.5-50 microL/mL in seven cases.