Stakeholders of the Online Pharmaceutical Market

During the past two decades, the pharmacy supply chain has developed a new segment besides traditional “brick and mortar” pharmacies. The expansion of the internet, consumer experience in online purchases, the ease of mail order trade, and distance selling have facilitated the growth of the internet pharmacy landscape. Changes in health-seeking behavior, patient empowerment, and openness to self-diagnosis and self-treatment have also contributed to the phenomenon and were further facilitated by the pandemic. Various types of online medicinal product sellers have been published previously, however, authors have classified online pharmacies mainly according to legality and patient safety considerations. As online pharmacies show great diversity, no distinct categories can be specified, rather pharmacies on the web can be categorized by multiple aspects. Admittedly, consumer preferences, regulatory environment, and legitimacy of operation are key influencing factors. In this chapter, key aspects of categorization and nomenclature are discussed to profile different vendors on the internet

Safety and risks of CBD oils purchased online: unveiling uncertain quality and vague health claims

Introduction: The unmet need for highly effective, naturally derived products with minimal side effects results in the over-popularity of ever-newer medicinal plants. In the middle of 2010, products containing cannabidiol (CBD), one of the special metabolites of Cannabis sativa , started to gain popularity. For consumers and healthcare providers alike, the legal context surrounding the marketing of CBD products is not entirely clear, and the safety of using some products is in doubt. Companies in the online medicinal product market profit from the confusion around CBD oils

Variable Star Classification with a Multiple-input Neural Network

In this experiment, we created a Multiple-Input Neural Network, consisting of convolutional and multilayer neural networks. With this setup the selected highest-performing neural network was able to distinguish variable stars based on the visual characteristics of their light curves, while taking also into account additional numerical information (e.g., period, reddening-free brightness) to differentiate visually similar light curves. The network was trained and tested on Optical Gravitational Lensing Experiment-III (OGLE-III) data using all OGLE-III observation fields, phase-folded light curves, and period data. The neural network yielded accuracies of 89%-99% for most of the main classes (Cepheids, delta Scutis, eclipsing binaries, RR Lyrae stars, Type-II Cepheids), only the first-overtone anomalous Cepheids had an accuracy of 45%. To counteract the large confusion between the first-overtone anomalous Cepheids and the RRab stars we added the reddening-free brightness as a new input and only stars from the LMC field were retained to have a fixed distance. With this change we improved the neural network's result for the first-overtone anomalous Cepheids to almost 80%. Overall, the Multiple-input Neural Network method developed by our team is a promising alternative to existing classification methods

An UXor among FUors: Extinction-related Brightness Variations of the Young Eruptive Star V582 Aur

V582 Aur is an FU Ori-type young eruptive star in outburst since similar to 1985. The eruption is currently in a relatively constant plateau phase, with photometric and spectroscopic variability superimposed. Here we will characterize the progenitor of the outbursting object, explore its environment, and analyze the temporal evolution of the eruption. We are particularly interested in the physical origin of the two deep photometric dips, one that occurred in 2012 and one that is ongoing since 2016. We collected archival photographic plates and carried out new optical, infrared, and millimeter-wave photometric and spectroscopic observations between 2010 and 2018, with a high sampling rate during the current minimum. Besides analyzing the color changes during fading, we compiled multiepoch spectral energy distributions and fitted them with a simple accretion disk model. Based on pre-outburst data and a millimeter continuum measurement, we suggest that the progenitor of the V582 Aur outburst is a low-mass T Tauri star with average properties. The mass of an unresolved circumstellar structure, probably a disk, is 0.04M(circle dot). The optical and near-infrared spectra demonstrate the presence of hydrogen and metallic lines, show the CO band head in absorption, and exhibit a variable Ha profile. The color variations strongly indicate that both the similar to 1 yr long brightness dip in 2012 and the current minimum since 2016 are caused by increased extinction along the line of sight. According to our accretion disk models, the reddening changed from A(V) = 4.5 to 12.5mag, while the accretion rate remained practically constant. Similarly to the models of the UXor phenomenon of intermediate- and low-mass young stars, orbiting disk structures could be responsible for the eclipses

Prospective Risk Assessment of Medicine Shortages in Europe and Israel: Findings and Implications

Introduction: While medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice. Methodology: A semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns. Results: The participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy. Conclusion: The study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe. © Copyright © 2020 Miljković, Godman, Kovačević, Polidori, Tzimis, Hoppe-Tichy, Saar, Antofie, Horvath, De Rijdt, Vida, Kkolou, Preece, Tubić, Peppard, Martinez, Yubero, Haddad, Rajinac, Zelić, Jenzer, Tartar, Gitler, Jeske, Davidescu, Beraud, Kuruc-Poje, Haag, Fischer, Sviestina, Ljubojević, Markestad, Vujić-Aleksić, Nežić, Crkvenčić, Linnolahti, Ašanin, Duborija-Kovačević, Bochenek, Huys and Miljković

Evaluation of the Online Pharmaceutical Market and Counterfeit Medicines: Development of a Risk Based Safety Mapping of Online Pharmaceutical Market

The Internet has revolutionized and changed our lives, communication and procurement practices and strategies. As the access to the Internet is increasing, the use of Internet to seek health information is also expending. Population based surveys found in the U.S. that 72% of the online population, while in Europe 71% of Internet users searched for health information at least once in the previous 12 months. However, consumers turn to the Internet today for not only just retrieving health information but to self-diagnose and obtain various health services or products. According to an early definition by Fung et al, an online pharmacy is an internet-based vendor (legal or illegal) that sells medicines and may operate as an independent Internet-only site, online branch of "brick-and-mortar" pharmacy, or sites representing partnership among pharmacies. Briefly, an online pharmacy is a website that offers to deliver, distribute, or dispense medications on the Internet direct to consumers. Internet supply of pharmaceuticals has developed in numerous ways and according to different models in each part of the world due to diverse regulatory, economic and cultural environments. In the United States the Internet pharmacy market is mainly prescription based, while in Europe this segment is forming according to a non-prescription based model. As Internet pharmacies can be accessed globally, thus the legislative and economic perspectives should be considered in every country worldwide

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

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

Probing the Interactions of 31 Mycotoxins with Xanthine Oxidase: Alternariol, Alternariol-3-Sulfate, and α-Zearalenol Are Allosteric Inhibitors of the Enzyme

Mycotoxins are frequent toxic contaminants in foods and beverages, causing a significant health threat. Interactions of mycotoxins with biotransformation enzymes (e.g., cytochrome P450 enzymes, sulfotransferases, and uridine 50 -diphospho-glucuronosyltransferases) may be important due to their possible detoxification or toxic activation during enzymatic processes. Furthermore, mycotoxin-induced enzyme inhibition may affect the biotransformation of other molecules. A recent study described the strong inhibitory effects of alternariol and alternariol-9-methylether on the xanthine oxidase (XO) enzyme. Therefore, we aimed to test the impacts of 31 mycotoxins (including the masked/modified derivatives of alternariol and alternariol-9-methylether) on XO-catalyzed uric acid formation. Besides the in vitro enzyme incubation assays, mycotoxin depletion experiments and modeling studies were performed. Among the mycotoxins tested, alternariol, alternariol-3-sulfate, and α-zearalenol showed moderate inhibitory actions on the enzyme, representing more than tenfold weaker impacts compared with the positive control inhibitor allopurinol. In mycotoxin depletion assays, XO did not affect the concentrations of alternariol, alternariol-3-sulfate, and α-zearalenol in the incubates; thus, these compounds are inhibitors but not substrates of the enzyme. Experimental data and modeling studies suggest the reversible, allosteric inhibition of XO by these three mycotoxins. Our results help the better understanding of the toxicokinetic interactions of mycotoxins