Introduction: Ecstasy (MDMA) is a popular recreational drug, but its illegal production and trade in the Netherlands have developed into a serious public order and ecological problem which endanger and question the harm reduction approach of the Dutch ecstasy policy.Methods: The market characteristics, adverse health effects, risk profile, and link to criminal activity of ecstasy were reviewed.Results: Ecstasy is often used in combination with other substances (i.e. polydrug use). Compared to several other illicit drugs and alcohol, ecstasy has a very low abuse and dependence liability and, as yet, there is little evidence of long-term harm. A potential health risk associated with ecstasy is acute hyperthermia, however this occurs at an unknown incidence rate and seems to be more prevalent when ecstasy is consumed in combination with heavy exercise at high ambient temperatures or when used in combination with other substances, including alcohol. Organized crime related to the production and trafficking of ecstasy in the Netherlands is a growing problem.Conclusions: This review provides a science-based summary that can be used to assist the public and political debate surrounding future Dutch ecstasy policy to reduce ecstasy-related organized crime while maintaining the principle of harm reduction.
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In this thesis several studies are presented that have targeted decision making about case management plans in probation. In a case management plan probation officers describe the goals and interventions that should help offenders stop reoffending, and the specific measures necessary to reduce acute risks of recidivism and harm. Such a plan is embedded in a judicial framework, a sanction or advice about the sanction in which these interventions and measures should be executed. The topic of this thesis is the use of structured decision support, and the question is if this can improve decision making about case management plans in probation and subsequently improve the effectiveness of offender supervision. In this chapter we first sketch why structured decision making was introduced in the Dutch probation services. Next we describe the instrument for risk and needs assessment as well as the procedure to develop case management plans that are used by the Dutch probation services and that are investigated in this thesis. Then we describe the setting of the studies and the research questions, and we conclude with an overview of this thesis.
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Aims: Prescribing medication is a complex process that, when done inappropriately, can lead to adverse drug events, resulting in patient harm and hospital admissions. Worldwide cost is estimated at 42 billion USD each year. Despite several efforts in the past years, medication-related harm has not declined. The aim was to determine whether a prescriber-focussed participatory action intervention, initiated by a multidisciplinary pharmacotherapy team, is able to reduce the number of in-hospital prescriptions containing ≥1 prescribing error (PE), by identifying and reducing challenges in appropriate prescribing. Methods: A prospective single-centre before- and after study was conducted in an academic hospital in the Netherlands. Twelve clinical wards (medical, surgical, mixed and paediatric) were recruited. Results: Overall, 321 patients with a total of 2978 prescriptions at baseline were compared with 201 patients with 2438 prescriptions postintervention. Of these, m456 prescriptions contained ≥1 PE (15.3%) at baseline and 357 prescriptions contained ≥1 PEs (14.6%) postintervention. PEs were determined in multidisciplinary consensus. On some study wards, a trend toward a decreasing number of PEs was observed. The intervention was associated with a nonsignificant difference in PEs (incidence rate ratio 0.96, 95% confidence interval 0.83–1.10), which was unaltered after correction. The most important identified challenges were insufficient knowledge beyond own expertise, unawareness of guidelines and a heavy workload. Conclusion: The tailored interventions developed with and implemented by stakeholders led to a statistically nonsignificant reduction in inappropriate in-hospital prescribing after a 6-month intervention period. Our prescriber-focussed participatory action intervention identified challenges in appropriate in-hospital prescribing on prescriber- and organizational level.
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In this proposal, a consortium of knowledge institutes (wo, hbo) and industry aims to carry out the chemical re/upcycling of polyamides and polyurethanes by means of an ammonolysis, a depolymerisation reaction using ammonia (NH3). The products obtained are then purified from impurities and by-products, and in the case of polyurethanes, the amines obtained are reused for resynthesis of the polymer. In the depolymerisation of polyamides, the purified amides are converted to the corresponding amines by (in situ) hydrogenation or a Hofmann rearrangement, thereby forming new sources of amine. Alternatively, the amides are hydrolysed toward the corresponding carboxylic acids and reused in the repolymerisation towards polyamides. The above cycles are particularly suitable for end-of-life plastic streams from sorting installations that are not suitable for mechanical/chemical recycling. Any loss of material is compensated for by synthesis of amines from (mixtures of) end-of-life plastics and biomass (organic waste streams) and from end-of-life polyesters (ammonolysis). The ammonia required for depolymerisation can be synthesised from green hydrogen (Haber-Bosch process).By closing carbon cycles (high carbon efficiency) and supplementing the amines needed for the chain from biomass and end-of-life plastics, a significant CO2 saving is achieved as well as reduction in material input and waste. The research will focus on a number of specific industrially relevant cases/chains and will result in economically, ecologically (including safety) and socially acceptable routes for recycling polyamides and polyurethanes. Commercialisation of the results obtained are foreseen by the companies involved (a.o. Teijin and Covestro). Furthermore, as our project will result in a wide variety of new and drop-in (di)amines from sustainable sources, it will increase the attractiveness to use these sustainable monomers for currently prepared and new polyamides and polyurethanes. Also other market applications (pharma, fine chemicals, coatings, electronics, etc.) are foreseen for the sustainable amines synthesized within our proposition.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
