Quality of dorzolamide hydrochloride and timolol maleate containing eye drops distributed online.

Patient safety risks associated with the online purchase of medications, especially in case of ophthalmic preparations, are significant. Our study aimed to carry out quality assessment of dorzolamide hydrochloride (DZA) and timolol maleate (TIM) eye drops preserved with benzalkonium chloride (BAC) via online test purchases. Three samples were purchased online, while control preparations were acquired through authorized national drug supply chain. Our method was based on the International Pharmaceutical Federation (FIP) Inspection Checklist and integrated the evaluation of packaging and labelling. Sterility was established according to the European Pharmacopoeia (Ph. Eur.), while qualitative and quantitative quality was assessed with high-performance liquid chromatographic (HPLC) analysis. Several signs of falsification were recognized upon visual inspection of the online samples. All the products were clear, colourless, slightly viscous solutions. They were free from visible contaminants. The samples were sterile as no evidence of microbial growth was found. A quick and inexpensive HPLC analysis, optimized by the authors showed that active ingredients and the preservative deviated significantly (p < 0,05) with more than 10% from the values stated on the labels for at least one component (DZA: 99.3-113.1%, TIM: 112.8-139.2%, BAC: 82.4-97.7%). Development of comprehensive and reliable quality assessment methods are vital to increase public safety of pharmaceutical products sold online. A complex approach, integrating visual inspection, labelling assessment, microbiological analysis coupled with qualitative and quantitative methods provide a most reliable method. Due to its limited feasibility and cost-effectiveness, raising public awareness and limiting illegal online sellers should be the primary approaches to protect patients from substandard and falsified medicinal products sold via the internet. Particularly important for health professionals to understand this market and its public health concern, and to raise patient awareness of the risks associated with uncontrolled online purchase of medication.

Cost-effectiveness analysis of invasive EEG monitoring in drug-resistant epilepsy.

PURPOSE: Our aim was to determine the cost-effectiveness of two intracranial electroencephalography (iEEG) interventions: 1) stereoelectroencephalography (SEEG) and 2) placement of subdural grid electrodes (SDGs) both followed by resective surgery in patients with drug-resistant, partial-onset epilepsy, compared with medical management (MM) in Hungary from payer's perspective. METHODS: The incremental health gains and costs of iEEG interventions have been determined with a combination of a decision tree and prevalence Markov process model over a 30-year time horizon in a cost-utility analysis (CUA). To address the effect of parameter uncertainty on the incremental cost-effectiveness ratio (ICER), deterministic and probabilistic sensitivity analyses were performed. RESULTS: Our results showed that both SEEG and SDG interventions represent a more expensive but more effective strategy than MM representing the current standard of care. The total discounted cost of SEEG and SDG were € 32,760 and € 25,028 representing € 18,108 and € 10,375 additional cost compared with MM, respectively. However, they provide an additional 3.931 (in SEEG group) and 3.444 quality-adjusted life years (QALYs; in SDG group), correspondingly. Thus, the ICER of SEEG is € 4607 per QALY gain, while the ICER for SDG is € 3013 per QALY gain, compared with MM. At a cost-effectiveness threshold of € 41,058 per QALY in Hungary, both subtypes of iEEG interventions are cost-effective and provide good value for money. SIGNIFICANCE: Because of the high cost of implanting electrodes and monitoring, the invasive EEG for patients with refractory epilepsy is currently not available in the Hungarian national healthcare system. Our study demonstrated that these procedures in Hungary are cost-effective compared with the MM. As a result, the introduction of iEEG interventions to the reimbursement list of the National Health Insurance Fund Administration was initiated.

Consumers Turning to the Internet Pharmacy Market: Cross-Sectional Study on the Frequency and Attitudes of Hungarian Patients Purchasing Medications Online.

BACKGROUND: During the past two decades, the internet has become an accepted way to purchase products and services. Buying medications online are no exception. Besides its benefits, several patient safety risks are linked to the purchase of medicines outside the traditional supply chain. Although thousands of internet pharmacies are accessible on the web, the actual size of the market is unknown. Currently, there is limited data available on the use of internet pharmacies, the number, and attitude of people obtaining medications and other health products from the internet. OBJECTIVE: This study aims to gather information on the frequency and attitudes of patients purchasing medications online in a nationally representative sample of outpatients. Attitudes towards main supply chain channels, perceived benefits, and disadvantages of influencing online medication purchase are evaluated. METHODS: A cross-sectional explorative study using a personally administered survey was conducted in a representative sample of Hungarian outpatients in 2018. RESULTS: A total of 1055 outpatients completed the survey (response rate 77.23%). The mean age was 45 years, and 456 (43.22%) reported having chronic health conditions. The majority (872/1055, 82.65%) of the respondents were aware that medications could be obtained online, but only 44 (4.17%) used the internet for previous medication purchases. Attitudes towards the different pharmaceutical supply chain retail channels showed significant differences (P<.001), respondents accepted retail pharmacy units as the most appropriate source of medications while rejected internet pharmacies. Respondents were asked to evaluate 9 statements regarding the potential benefits and disadvantages about the online medicine purchase, and based on the computed relative attitude rate there is a weak still significant tendency toward rejection (P<.001). Correspondence of demographic factors, internet usage behavior, and prospective online drug purchase attitude was evaluated. Respondents who use the internet more and purchase goods online will be more likely to buy medications online. Furthermore, youth and education will determine the medication purchase behavior. CONCLUSIONS: Many patients will purchase medications on the internet in the future. Currently, there is an increased risk of patients buying products from illegal sites because these dominate the global online pharmacy market. Consequently, improved patient-provider communication and promotion campaigns are needed to inform the public about the safe use of internet pharmacies, as these initiatives can directly prevent patient safety threats.

[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.

Evaluating aspects of online medication safety in long-term follow-up of 136 Internet pharmacies: illegal rogue online pharmacies flourish and are long-lived.

BACKGROUND: A growing number of online pharmacies have been established worldwide. Among them are numerous illegal websites selling medicine without valid medical prescriptions or distributing substandard or counterfeit drugs. Only a limited number of studies have been published on Internet pharmacies with regard to patient safety, professionalism, long-term follow-up, and pharmaceutical legitimacy verification. OBJECTIVE: In this study, we selected, evaluated, and followed 136 Internet pharmacy websites aiming to identify indicators of professional online pharmacy service and online medication safety. METHODS: An Internet search was performed by simulating the needs of potential customers of online pharmacies. A total of 136 Internet pharmacy websites were assessed and followed for four years. According to the LegitScript database, relevant characteristics such as longevity, time of continuous operation, geographical location, displayed contact information, prescription requirement, medical information exchange, and pharmaceutical legitimacy verification were recorded and evaluated. RESULTS: The number of active Internet pharmacy websites decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months and only 67 monitored websites (49.3%) were accessible at the end of the four-year observation period. However, not all operated continuously, as about one-fifth (31/136) of all observed online pharmacy websites were inaccessible provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any contact details, while only 59 (43.4%) displayed all necessary contact information on the website. We found that the declared physical location claims did not correspond to the area of domain registration (according to IP address) for most websites. Although the majority (120/136, 88.2%) of the examined Internet pharmacies distributed various prescription-only medicines, only 9 (6.6%) requested prior medical prescriptions before purchase. Medical information exchange was generally ineffective as 52 sites (38.2%) did not require any medical information from patients. The product information about the medicines was generally (126/136, 92.6%) not displayed adequately, and the contents of the patient information leaflet were incomplete in most cases (104/136, 76.5%). Numerous online operators (60/136, 44.1%) were defined as rogue Internet pharmacies, but no legitimate Internet-based pharmacies were among them. One site (0.7%) was yet unverified, 23 (16.9%) were unapproved, while the remaining (52/136, 38.2%) websites were not available in the LegitScript database. Contrary to our prior assumptions, prescription or medical information requirement, or the indication of contact information on the website, does not seem to correlate with "rogue pharmacy" status using the LegitScript online pharmacy verification standards. Instead, long-term continuous operation strongly correlated (P<.001) with explicit illegal activity. CONCLUSIONS: Most Internet pharmacies in our study sample were illegal sites within the definition of "rogue" Internet pharmacy. These websites violate professional, legal, and ethical standards and endanger patient safety. This work shows evidence that online pharmacies that act illegally appear to have greater longevity than others, presumably because there is no compelling reason for frequent change in order to survive. We also found that one in five websites revived (closed down and reopened again within four years) and no-prescription sites with limited medicine and patient information are flourishing.

[Preoperative embolisation of spinal metastases]. / A spinális metasztázisok preoperatív embolizációja.

In the management of spinal metastases bringing about neurological symptoms and signs, palliative surgical treatment plays an important role. The goals of surgery are preservation of neurological function especially that of the mobility, pain relief and local tumor control. Many of spinal metastases are hypervascularised, accordingly, preoperative embolisation offers logically improvement in technical realisation of surgery by means of reduction of intraoperative profuse bleeding. To prove this working hypothesis a retrospective analysis was performed. Results of preoperative transarterial embolisation of hypervascularised spinal tumours were worked up from 2000 to 2012. By means of 2 case presentations - to our knowledge, first in the Hungarian literature - the techniques of transarterial spinal embolisation of spinal metastases are described. Indications, complications and effect on intraoperative bleeding events of the embolisation procedure in these oncological cases are presented on the basis of literature search and of our own experience. The case analyses, based mainly on qualitative retrospective data, support the notion that histologically known spinal hypervascularised metastases or those found to be hypervascularised by MRI can be treated effectively by means of preoperative superselective embolisation without major risks of morbidity or mortality.

Analysis of pharmacovigilance databases for spontaneous reports of adverse drug reactions related to substandard and falsified medical products: A descriptive study.

Introduction: The public health threat of substandard and falsified medicines has been well known in the last two decades, and several studies focusing on the identification of products affected and preventing consumption have been published. However, the number of these products reaching patients and causing health consequences and adverse drug reactions is not a well-researched area. Objectives: Our aim was to identify and describe the characteristics of cases that are related to adverse drug reactions potentially originating from counterfeit medication using publicly available pharmacovigilance data. Methods: A descriptive study was performed based on pharmacovigilance data retrieved from Individual Case Safety Reports (ICSRs) identified in the European Medicines Agency's EudraVigilance and FDA Adverse Event Reporting System (FAERS) databases in April 2022 using selected MedDRA preferred terms: counterfeit product administered, product counterfeit, product label counterfeit, product packaging counterfeit, suspected counterfeit product, adulterated product, product tampering, and suspected product tampering. ICSRs were analyzed by age and gender, by year of reporting, region of origin, reporter's profession, and severity of the outcome. The disproportionality method was used to calculate pharmacovigilance signal measures. Results: A total of 5,253 cases in the FAERS and 1,049 cases in the EudraVigilance database were identified, generally affecting middle-aged men with a mean age of 51.055 (±19.62) in the FAERS and 64.18% of the cases between 18 and 65 years, while the male to female ratios were 1.18 and 1.5. In the FAERS database, we identified 138 signals with 95% confidence interval including sildenafil (n = 314; PRR, 12.99; ROR, 13.04; RRR, 11.97), tadalafil (n = 200; PRR, 11.51; ROR, 11.55; RRR, 10.94), and oxycodone (n = 190; PRR, 2.47; ROR, 2.14; RRR, 2.47). While in the EV data 31, led by vardenafil (n = 16, PRR = 167.19; 101.71-274.84; 95% CI, RRR = 164.66; 100.17-270.66; 95% CI, ROR = 169.47; 103.09-278.60; 95% CI, p < 0.001), entecavir (n = 46, PRR = 161.26, RRR = 154.24, ROR = 163.32, p < 0.001), and tenofovir (n = 20, PRR = 142.10, RRR = 139.42, ROR = 143.74, p < 0.001). Conclusion: The application of pharmacovigilance datasets to identify potential counterfeit medicine ADRs can be a valuable tool in recognition of potential risk groups of consumers and the affected active pharmaceutical ingredients and products. However, the further development and standardization of ADR reporting, pharmacovigilance database analysis, and prospective and real-time collection of potential patients with health consequences are warranted in the future.

Development of Capsaicin-Containing Analgesic Silicone-Based Transdermal Patches.

Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose capsaicin. Release properties were measured in Franz diffusion cell and continuous flow-through cell approaches. Capsaicin was detected with HPLC-UV and UV spectrophotometry. Raman spectroscopy was conducted on human skin samples exposed to the TTS. A surgical incision or carrageenan injection was performed on one hind paw of male Wistar rats. TTSs were applied to the epilated dorsal skin. Patches were kept on the animals for 6 h. The thermal hyperalgesia and mechanical pain threshold of the hind paws were detected. Patches exhibited controlled, zero-order kinetic capsaicin release. According to the Raman mapping, capsaicin penetrated into the epidermis and dermis of human skin, where the target receptors are expressed. The thermal pain threshold drop of the operated rat paws was reversed by capsaicin treatment compared to that of animals treated with control patches. It was concluded that our modified silicone-polymer-based capsaicin-containing TTS is suitable for the relief of traumatic and inflammatory pain.

Pilot study for the characterization of pharmacogenetically relevant CYP2D6, CYP2C19 and ABCB1 gene polymorphisms in the Hungarian population.

Polymorphisms of CYP450 metabolizer enzymes and transport proteins play crucial roles in the inter-individual variability of drug efficiency. The aim of our study was to predict the frequency of functional variants of CYP2D6, CYP2C19 and ABCB1 genes in the Hungarian population. One hundred twelve unrelated healthy subjects donated DNA sample in the study. ABCB1 C3435T and G2677T/A single-nucleotide polymorphisms (SNPs) were determined by LightCycler polymerase chain reaction. Because only limited amount of data is available on the rare allelic variants of CYP2D6 in the European populations, our study applied an expanded set of CYP2D6 and CYP2C19 alleles by using AmpliChip test. Our results show that the CYP2D6 phenotypes were 1.9% ultra-rapid metabolizer, 6.5% intermediate metabolizer (IM), 8.3% poor metabolizer (PM) and 83.3% extensive metabolizer (EM), and the CYP2C19 phenotypes were 1.8% PM, 31.2% IM and 67% EM. The prevalence of the commonly observed CYP2D6 and CYP2C19 alleles in our study corresponds with that of other European populations. Nevertheless, our study confirms that extending the CYP2D6 allele set with loss-of-function variants such as CYP2D6*7, *9, *41 is worth considering. Frequency of the wild type ABCB1 3435C was 42.8% whereas the prevelance of 2677 G was 50.4%. Although frequency data of G2677T/A SNP in the European area are limited, some discrepancies with other studies were found.

Survey of workflow and cost implications of decommissioning regarding the Falsified Medicines Directive in Hungarian hospital pharmacies.

OBJECTIVES, SETTING AND PARTICIPANTS: In July 2011, the EU adopted the Falsified Medicines Directive (FMD) primarily aiming to prevent the infiltration of falsified medicines into the legitimate supply chain. Our aim was to measure the cost elements of FMD implementation and operation using an internationally adaptable tool among Hungarian hospital pharmacies. DESIGN: A 41-item questionnaire was developed to evaluate the implementation process and associated cost consequences leading up to February 2019, and the stabilisation period. RESULTS: Our representative data are supported by the high response rate, as 44.8% of the Hungarian hospital pharmacies have completed the survey. Human resource requirements related to decommissioning activities were measured as working hours and were expressed in full time equivalent (FTE). We have found an increased workload with extra 0.25 pharmacist and 0.75 technician FTE/institution at the end of the stabilisation period. The entire infrastructural and IT implementation costs were determined as €2173, on average (SD: €3366) and the median was €1506 (range: €0-€20 723). The total IT investment cost per institution was valued at €1410 (SD: €335). We identified a positive correlation (R=0.663) in consideration of the costs, the number of beds and the number of hospital locations with a multivariate linear regression model. At the time of our survey, 76.7% of the respondents experienced drug shortages, 58.1% reported suspected increase in drug costs regarding serialised medications, and 53.5% noticed an increase in packaging size. CONCLUSIONS: Notably, our research is the first complex study depicting FMD cost implications in the hospital pharmacy sector in Central Europe, indicating decommissioning significantly impacted workflow referencing human resources and IT.

Optimization of bioassay method for the quantitative microbiological determination of amphotericin B.

The aim of this study was to find the optimal bioassay parameters for the quantitative analysis of an amphotericin B nasal spray solution as the bioassay conditions recommended by the Ph. Eur. 6. were less sensitive and were only applicable for the measurement of a narrow concentration range, which makes the method unsuitable in case of a stability test. We evaluated five commonly used assay media with Candida albicans and Saccharomyces cerevisiae as test organisms. Our results showed that Mueller Hinton Agar supplemented with 2% glucose and 0.5 microg ml(-1) methylene blue inoculated with C. albicans gave the best bioassay circumstance as a wide concentration range (1.54-60.0 microg ml(-1) amphotericin B) could be measured and the inhibition zone borders were distinct and easy to read.

[Attitude of patients and customers toward on-line purchase of drugs--a Hungarian survey by community pharmacies]. / Internetes gyógyszervásárlás megítélése a gyógyszertárba járó fogyasztók, betegek körében.

As internet is now available to nearly everyone in Hungary, the accessibility of websites offering pharmaceutical products is also increasing. The national and international regulation of these sites is currently an unsolved problem worldwide, thus potentially harmful, counterfeit and prescription only medicines are easily accessible on the market. We aimed to measure and estimate the current situation of the ordering of online medicines. In 5 Hungarian cities 434 self-administered questionnaires were collected in community pharmacies. Our results show that 6.2% of the respondents have already ordered drugs or dietary supplements online and approximately same amount of people are considering this option in the near future. Based on our survey mostly the educated, the 30-49 year old people and women are likely to buy drugs online. Every fifth respondent reported willingness to buy drugs online from abroad if lower prices were offered. Most people do not know that the quality of medicines purchased online could be different from the ones purchased from community pharmacies. We would like to draw attention of healthcare professionals to the rising popularity and potential risks of drugs available online.

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.

Shedding light on the HTA consultancy market: Insights from Poland.

Research on health technology assessment (HTA) from a policy perspective typically examines public HTA bodies, with little attention devoted to how manufacturers develop their evidence submissions. Taking Poland as a crucial case, we explored the market of HTA consultancy firms which assist drug manufacturers in developing these submissions, called HTA reports. We reviewed 318 HTA reports from 2012 to 2015, data from the Polish National Company Registry, the content of HTA consulting firms' websites, and appraisal reports developed by the Polish HTA body. We identified HTA consultancy firms which developed 96-98% HTA reports. We found that the transparency of information about the authors of HTA reports provided by the HTA body had improved between 2012 and 2015. Six companies with market shares from 10 to 30% dominated the market. The market size was estimated to be 5-6 million EUR annually. HTA consultancies had a broad service portfolio related to preparation of HTA reports. Over 90% of HTA reports did not meet the official minimum quality requirements, and only half of the resubmissions took into account remarks made by the HTA body. Our study provides insights into the structure, evolution and role of the for-profit HTA consultancy market as a crucial part of the public HTA system. This raises important policy points about transparency and regulation at the intersection of public and private sectors in HTA.

[Postoperative application of amphotericin B nasal spray in chronic rhinosinusitis with nasal polyposis. Can recidive polyposis be prevented?]. / Amphotericin B-tartalmú orrspray posztoperatív alkalmazása orrpolyposissal járó krónikus rhinosinusitis eseteiben. Megelozheto-e a recidíva?

UNLABELLED: Chronic rhinosinusitis affects 1-4% of the adult population. The aetiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE type) immune response. AIM: If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. METHODS: To check on this assumption, the authors conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; one group of them (group A, 14 randomly selected patients) was treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group (group B, 16 randomly selected patients) received a nasal spray lacking amphotericin B. The results were evaluated with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which evaluates changes in the symptoms), the life-quality test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and one year postoperatively. RESULTS: The CT scores of the group A patients exhibited wide scattering without signs of recovery one year after the operation. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant in relation to group A. Both the SNAQ-11 test and the life-quality test revealed a significant improvement in each group, but the degrees of change in these tests did not significantly differ between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. CONCLUSION: These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in CT scores, clinical symptoms, or quality of life. The more favourable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study the authors discuss the available data on the fungal theory. They critically analyse the contradictory observations of 7 recent clinical studies.

[Chemical and microbiological aspects of the quantitative analysis of amphotericin B]. / Amfotericin B tartalmú készítmények kvantitatív analízisének kémiai és mikrobiológiai vonatkozásai.

Amphotericin B can be determined by chemical (HPLC, spectrophotometry) and microbiological (bioassay) methods. The utilization of both during a stability test can give more detailed information about the activity and concentration change of amphotericin B solutions. Previously published HPLC methods do not lay stress on the separation of by-constituents present in the substance. We have also observed that the bioassay conditions described in the Ph. Eur. 6. are not suitable for the measurement of concentration change experienced during a stability test. The aim of our study was to optimize the chemical and microbiological methods. We have improved the eluent system based on earlier HPLC methods for the separation of the main heptaene and the minor tetraene by-constituents in Fungizone (Bristol-Myers Squibb). The most optimal bioassay conditions were determined where a relatively wide concentration range can be measured. With the improved methods both chemical and microbiological changes can be more accurately measured in our future stability tests.

A challenge for healthcare but just another opportunity for illegitimate online sellers: Dubious market of shortage oncology drugs.

INTRODUCTION: Drug shortages mean a challenge to healthcare systems. Exposed patients or health care providers may seek alternative resources for these products online. The purpose of our study was to analyze the online availability of oncology shortage drugs at national and at international levels in 2014 and 2016. METHODS: We tested the online accessibility of oncology shortage drugs by simulating the Internet search method of patients. Search results were evaluated according to operational, distributional, and patient safety characteristics. RESULTS: In 2014 and 2016 all (100%) antineoplastic agents affected by shortages were available on the Internet without medical prescription. The number of relevant websites among search engine results has decreased from 112 to 98, while online vendors actually offering oncology shortage drugs for sale has risen from 66.1% to 80.6% within relevant websites in the two evaluated years. None of the online sellers were classified as legitimate or accredited by LegitScript and VIPPS online pharmacy verification databases. CONCLUSION: According to our findings shortage oncology drugs are widely available online. To manage shortages and illegal Internet trade national and international standardized shortage reporting and information systems, regularly updated Internet pharmacy verification databases are needed. As well, institutional procurement and medication use review policies are required.

[Medicinal plant research and phytochemical traditions of Pécs]. / Pécsi gyógynövenykutatási és fitokémiai hagyományok.

The authors have summarized the local history of pharmacobotany, phytochemistry and pharmacognosy remembering Szabolcs Nyiredy, the honorary professor of Pécs University.

[Stability testing of amphotericin B nasal spray solutions with chemical and biological analysis]. / Amfotericin B tartalmú orrspray oldat stabilitásvizsgálata biológiai es kémiai detektálással.

Recent studies have shown that the presence of fungal cells in the nasal mucosa may play an important role in the development of chronic rhinosinusitis with nasal polyps. In 2006 a pilot clinical trial was organized by the Department of Otorhinolaryngology, Head and Neck Surgery and the Pharmaceutical Institute of the Medical University of Pécs for the treatment of patients with chronic rhinosinusitis with nasal polyps. In our study we investigated the stability of the 5 mg/ml amphotericin B solutions (Fungizone) with chemical (spectrophotometry) and biological (bioassay) detection. The effect of storage temperature and the addition of 5% glucose was evaluated on the stability of the solutions for three months. The two detection methods showed different results. According to the chemical analysis the samples are considered relatively stable under all observed conditions (loss of concentration is: 14.2% at 20 degrees C and 4.5% at 4 degrees C). The bioassay shows complete loss of antifungal activity after 35 days of storage at room temperature and notable decrease can be observed at 4 degrees C (glucose containing solution 17.6%; glucose free solution 37.2%). Storage temperature had significant effect (p < 0.05), while 5% glucose had no significant effect (p > 0.05) on the stability of the examined solutions. Bioassay is considered to be the official quantitative analytical method for the analysis of amphotericin B recommended by the European Pharmacopoeia 4. Thus we estimated the shelf life of the glucose-free solutions, being stored at 4 degrees C, to be 30 days in accordance with our bioassay results.