[Orphan drugs and drug pirates]. / Weesgeneesmiddelen en medicijnkapers.

The European Orphan Medicines Regulation, which came into effect in 2000, stimulates the development of medicines for rare diseases. The number of registered orphan medicines has increased from eight in 2000 to 169 in 2019; 38% of these are available in the Netherlands. The costs for orphan medicines in the Netherlands are increasing by 9% every year, and now amount to €272 million annually. There is, however, still no effective medication for thousands of rare diseases. The Orphan Regulation was intended for new orphan medicines, but some companies also use it for 'repurposing' of old agents, for which they also get 10 years exclusive market rights in the EU. The improper use of legislation has led to concern among patients, doctors, and medical insurance companies. The Netherlands Council for Public Health and Society and MPs in the lower house of the Netherlands parliament have proposed measures for tackling the high prices of medicines and Mr. Bruins, the former Minister of Health, wanted to propose legislative change in the EU. The EU 'pharmaceutical incentive review' offers the possibility to revise the current rules.

Flow cytometric analysis of extracellular vesicle subsets in plasma: impact of swarm by particles of non-interest.

Essentials Extracellular vesicles (EVs) in biological fluids are promising biomarkers for disease. Fluorescence-based flow cytometric analysis is suitable to detect low abundant EV subsets. Particles of non-interest can induce false-positive light scatter and fluorescent signals. Interference of particles of non-interest can be monitored by analyzing serial dilutions. SUMMARY: Background Extracellular vesicles (EVs) in plasma are increasingly being recognized as potential biomarkers. EV analysis for diagnostic purposes should be robust and should allow analysis of EV subsets with a wide range of abundance and in a large number of patient samples. Flow cytometry offers possibilities to meet these criteria, as it allows multiparameter analysis of individual EVs. However, analysis of plasma EVs is challenging, because of their size and heterogeneity, and the presence of other submicrometer-sized particles in plasma that could interfere with EV analysis. Objectives To explore whether fluorescence-based flow cytometric analysis of EV subsets is suitable when the EVs of interest are present in low abundance in a background of non-labeled or differently labeled EVs and particles. Methods Fluorescently labeled EVs of interest were spiked at different ratios in full plasma, purified plasma components, or (non-)fluorescent polystyrene beads, and subsequently analyzed by flow cytometry with fluorescence threshold triggering. Results We found that light scatter detection of low-abundance or rare EV subsets during fluorescence threshold triggering was severely affected by particles of non-interest, owing to coincidence and swarming. Importantly, we show that interfering particles labeled with different fluorophores induced false-positive fluorescent signals on the particles of interest. These unwanted effects could only be discerned and controlled by performing serial dilutions and analyzing light scatter and fluorescence parameters. Conclusions We demonstrate how particles of non-interest in plasma can impact on the light scatter and fluorescence detection of low-abundance EVs of interest during fluorescence-based flow cytometric analysis, and provide a means to prevent erroneous data interpretation.

The role of microRNA in nutritional control.

MicroRNAs (miRNAs) are one of a growing class of noncoding RNAs that are involved in the regulation of a wide range of metabolic processes including cellular differentiation, cell proliferation and apoptosis. The generation of miRNA is regulated in complex ways, for example by small interfering RNAs (small nucleolar and nuclear RNAs) and various other metabolites. This complexity of control is likely to explain how a relatively small part of the DNA that codes for proteins has enabled the evolution of such complex organisms as mammals. Non-protein-coding DNA is therefore thought to carry the memory of early evolutionary steps that led to progressively complex metabolic controls. Clinically, miRNAs are becoming increasingly important following the recognition that some congenital abnormalities can be traced to defects in miRNA processing. The potential for manipulating metabolism and affecting disease processes by the pharmaceutical or biological targeting of specific miRNA pathways is now being tested. miRNAs are also released into the extracellular milieu after packaging by cells into nano-sized extracellular vesicles. Such vesicles can be taken up by adjacent and possibly more distant cells, thereby allowing coordinated intercellular communication in specific tissues. Extracellular miRNAs found in the blood stream may also serve as novel biomarkers for both diagnosing specific forms of cancer and assessing the likelihood of metastasis, and as powerful prognostic indices for various cancers. Here, we discuss the role of intracellular and extracellular miRNAs in nutritional control of various (patho)physiological processes. In this review, we provide an update of the presentations from the 25th Marabou Symposium (Stockholm, 14-16 June 2013) entitled 'Role of miRNA in health and nutrition', attended by 50 international experts

A training course in health technology assessment in Malaysia.

This article describes a 1-week training course in health technology assessment (HTA) presented in Malaysia by the Ministry of Health in 1996. Malaysia established an HTA unit in the Ministry of Health in 1995 and a National Health Technology Assessment Program in 1996. The purpose of the course was to develop HTA knowledge and skills in Malaysia, since these are largely lacking. The course consisted of didactic sessions and group work. Didactic sessions covered the principles of HTA. Group work was for the purpose of developing practical skills, and was based on reports from HTA agencies, published articles, and candidates for assessment suggested by course participants. Course participants were a mix of physicians, nurses, hospital administrators, and Ministry of Health officials. Experiences in this course may be helpful to others who wish to organize training courses in developing countries.