Understanding and Fighting the Medicine Counterfeit Market

Medicine counterfeiting is a serious worldwide issue, involving networks of manufacture and distribution that are an integral part of industrialized organized crime. Despite the potentially devastating health repercussions involved, legal sanctions are often inappropriate or simply not applied. The difficulty in agreeing on a definition of counterfeiting, the huge profits made by the counterfeiters and the complexity of the market are the other main reasons for the extent of the phenomenon. Above all, international cooperation is needed to thwart the spread of counterfeiting. Moreover effort is urgently required on the legal, enforcement and scientific levels. Pharmaceutical companies and agencies have developed measures to protect the medicines and allow fast and reliable analysis of the suspect products. Several means, essentially based on chromatography and spectroscopy, are now at the disposal of the analysts to enable the distinction between genuine and counterfeit products. However the determination of the components and the use of analytical data for forensic purposes still constitute a challenge. The aim of this review article is therefore to point out the intricacy of medicine counterfeiting so that a better understanding can provide solutions to fight more efficiently against it.

Strategic behaviours in healthcare : evidence from primary care and pharmaceutical markets

We analyse the strategic behaviours of agents in a market through the appropriate¬ness of their skills to the market. If agents' skills are well adapted to market and they can reach their target, they will not need to adopt strategic behaviours. The agents will behave as selfish individuals. However, if their skills are not well adapted and they cannot attain their target alone, they will adopt strategic behaviours to reach their objectives. These behaviours will have a different impact on the utilities of other agents, depending on the skills and the objectives of the agent. If these agents need other agents to reach their objectives, they will behave as altruistic individuals who internalise the utilities of other agents in reaching their objectives and will adopt cooperative behaviours. However, if these agents fear that other agents could prevent them from reaching their target because they can foresee that the skills of other agents are better adapted than their own skills, the agents will then behave as predator individuals and will adopt destructive behaviours to attain their objective. It is in the interests of these agents to manipulate information to increase disorder and dissimulate their lack of skills. They will reproduce the strategies of animals that modify their appearance to escape predators or simulate being bait to attract their prey. These agents will seek to induce chaos into the behaviours of other agents to amplify the impact of their strategies. The appropriateness of skills to the market allows an understanding of the emer-gence of networks and associated strategies. The members of a networks are inputs who are excluded when their costs are higher than their benefits. A network simul-taneously allows cooperation and selfish, predatory behaviours among its members. A network may adopt informational strategies when seeking to become the leader in a market or when it cannot survive. The creation of networks and the manipulation of information are two overlapping evolutionary strategies, with the first strategy favouring the second. In our model, an agent does not behave like a firm that aims only to maximise the profits of the firm but rather as a member of a network who adopts strategic behaviours as a function of the interests of this network. If his skills are well adapted to the market and he can innovate, he will not invest in erroneous input; in contrast, if his skills are not adapted, the agent will invest in the erroneous input of information into the market in order to survive. Therefore, when any informational asymmetries between the agents and their principals characterise the market, the price cannot be the main element that allows equilibrium to be reached in the market; instead, the appropriateness of skills to the market enables equilibrium. We will now apply these hypotheses to explain the strategic behaviours of physicians and pharmaceutical companies.

Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center.

Abstract Context. Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. Methods. A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. Results. We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. Conclusions. Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. "Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27-30 May 2014, Brussels, Belgium." Abstract 8, Clin Toxicol 2014;52(4):298.

Colloidal systems for the delivery of cyclosporin A to the anterior segment of the eye.

Due to the eye's specific anatomical and physiological conformation, the treatment of eye diseases is a real challenge for pharmaceutical therapy. The presence of efficient protective barriers (i.e., the conjunctival and corneal membranes) and protective mechanisms (i.e., blinking and nasolachrymal drainage) makes this organ particularly impervious to local drug therapy. To overcome these issues, numerous strategies have been envisioned using pharmaceutical technology. Many formulations currently on the market or still under development are emulsions or colloidal systems intended to enhance precorneal residence time and corneal penetration, causing a consequent increase in drug bioavailability after instillation. After a review of some recent developments in the field of cyclosporin A formulations for the eye, a novel micellar formulation of cyclosporine A based on a diblock methoxy-poly(ethylene glycol)-hexysubstituted poly(lactides) (MPEG-hexPLA) is described.

Market-Based Instruments for ecosystem services: institutional innovation or renovation?

Recent years have seen widespread experimentation with market-based instruments (MBIs) for the provision of environmental goods and ecosystem services. However, little attention has been paid to their design or to the effects of the underlying pro-market narrative on environmental policy instruments. The purpose of this article is to analyze the emergence and dissemination of the term "market-based instruments" applied to the provision of environmental services and to assess to what extent the instruments associated are genuinely innovative. The recommendation to develop markets can lead in practice to a variety of institutional forms, as we show it based on the example of payments for environmental services (PES) and biodiversity offsets, two very different mechanisms that are both presented in the literature as MBIs. Our purpose is to highlight the gap between discourse and practice in connection with MBIs.

Methods for detection and confirmation of Hematide?/peginesatide in anti-doping samples.

Since the 1990's, cheating athletes have abused substances to increase their oxygen transport capabilities; among these substances, recombinant EPO is the most well known. Currently, other investigational pharmaceutical products are able to produce an effect similar to EPO but without having chemical structures related to EPO; these are the synthetic erythropoiesis stimulating agents (ESAs). Peginesatide (also known as Hematide?) is being developed by Affymax and Takeda and, if approved by regulatory authorities, could soon be released on the international market. To detect potential athletic abuse of this product and deter athletes who consider cheating, we initiated a collaboration to implement a detection test for anti-doping purposes. Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. It is undetectable using current anti-doping tests due to its lack of sequence homology to EPO. To detect and deter potential abuse of peginesatide, we initiated an industry/antidoping laboratory collaboration to develop and validate screening and confirmation assays so that they would be available before peginesatide reaches the market. We describe a screening ELISA and a confirmation assay consisting of immune-purification followed by separation with SDS-PAGE and revelation with Western double blotting. Both assays can detect 0.5 ng/mL concentrations of peginesatide in blood samples, enabling detection for several days after administration of a physiologically relevant dose. This initial report describes experimental characterization of these assays, including testing with a blinded set of samples from a clinical study conducted in healthy volunteers.