Developing a new national MDMA policy:Results of a multi-decision multi-criterion decision analysis

BACKGROUND: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act (‘hard drugs’). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy. METHODS: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA). The experts collectively formulated policy instruments and rated their effects on 25 outcome criteria, including health, criminality, law enforcement and financial issues, thematically grouped in six clusters. RESULTS: The experts scored the effect of 22 policy instruments, each with between two and seven different mutually exclusive options, on 25 outcome criteria. The optimal policy model was defined by the set of 22 policy instrument options which gave the highest overall score on the 25 outcome criteria. Implementation of the optimal policy model, including regulated MDMA sales, decreases health harms, MDMA-related organised crime and environmental damage, as well as increases state revenues and quality of MDMA products and user information. This model was slightly modified to increase its political feasibility. Sensitivity analyses showed that the outcomes of the current MD-MCDA are robust and independent of variability in weight values. CONCLUSION: The present results provide a feasible and realistic set of policy instrument options to revise the legislation towards a rational MDMA policy that is likely to reduce both adverse (public) health risks and MDMA-related criminal burden

A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

Background: Low frequency sensorineural hearing loss (LFSNHL) is an uncommon clinical finding. Mutations within three different identified genes (DIAPH1, MYO7A, and WFS1) are known to cause LFSNHL. The majority of hereditary LFSNHL is associated with heterozygous mutations in the WFS1 gene (wolframin protein). The goal of this study was to use genetic analysis to determine if a small American family's hereditary LFSNHL is linked to a mutation in the WFS1 gene and to use VEMP and EcochG testing to further characterize the family's audiovestibular phenotype. Methods: The clinical phenotype of the American family was characterized by audiologic testing, vestibular evoked myogenic potentials (VEMP), and electrocochleography (EcochG) evaluation. Genetic characterization was performed by microsatellite analysis and direct sequencing of WFS1 for mutation detection. Results: Sequence analysis of the WFS1 gene revealed a novel heterozygous mutation at c.2054G>C predicting a p.R685P amino acid substitution in wolframin. The c.2054G>C mutation segregates faithfully with hearing loss in the family and is absent in 230 control chromosomes. The p.R685 residue is located within the hydrophilic C-terminus of wolframin and is conserved across species. The VEMP and EcochG findings were normal in individuals segregating the WFS1 c.2054G>C mutation. Conclusion: We discovered a novel heterozygous missense mutation in exon 8 of WFS1 predicting a p.R685P amino acid substitution that is likely to underlie the LFSNHL phenotype in the American family. For the first time, we describe VEMP and EcochG findings for individuals segregating a heterozygous WFS1 mutation.NIH grants DC04945 (V.A.S), DC006901 (V.A.S.) and P30 DC04661 (V.M. Bloedel Core)

Physical Stress, Not Biotic Interactions, Preclude an Invasive Grass from Establishing in Forb-Dominated Salt Marshes

Biological invasions have become the focus of considerable concern and ecological research, yet the relative importance of abiotic and biotic factors in controlling the invasibility of habitats to exotic species is not well understood. Spartina species are highly invasive plants in coastal wetlands; however, studies on the factors that control the success or failure of Spartina invasions across multiple habitat types are rare and inconclusive.We examined the roles of physical stress and plant interactions in mediating the establishment of the smooth cordgrass, Spartina alterniflora, in a variety of coastal habitats in northern China. Field transplant experiments showed that cordgrass can invade mudflats and low estuarine marshes with low salinity and frequent flooding, but cannot survive in salt marshes and high estuarine marshes with hypersaline soils and infrequent flooding. The dominant native plant Suaeda salsa had neither competitive nor facilitative effects on cordgrass. A common garden experiment revealed that cordgrass performed significantly better when flooded every other day than when flooded weekly. These results suggest that physical stress rather than plant interactions limits cordgrass invasions in northern China.We conclude that Spartina invasions are likely to be constrained to tidal flats and low estuarine marshes in the Yellow River Delta. Due to harsh physical conditions, salt marshes and high estuarine marshes are unlikely to be invaded. These findings have implications for understanding Spartina invasions in northern China and on other coasts with similar biotic and abiotic environments

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies

Adverse effects of levamisole in cocaine users: a review and risk assessment.

The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users

Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB

In the Netherlands, γ-hydroxybutyric acid (GHB) was recently banned, but γ-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB. Pure GBL is per unit of volume about threefold stronger and therefore threefold more potent than currently used GHB-preparations in the Netherlands. Like GHB, GBL use hardly leads to organ toxicity, although, as with GHB, frequent GBL use may lead to repeated comas that may result in residual impairments in cognitive function and memory. Little is known about the prevalence of GBL use in Europe, but the recent increase in improper trading in GBL confirms that users of GHB gradually switch to the use of GBL. This shift may result in an increase in the number GBL dependent users, because the dependence potential of GBL is as great as that of GHB. Severe withdrawal symptoms and a high relapse rate are seen following cessation of heavy GBL use. GBL-dependent users seem to be severe (dependent, problematic) GHB users who started using GBL, the legal GHB substitute. Subjects who are solely dependent to GBL are rarely reported. About 5-10% of the treatment seeking GHB dependent subjects also use GBL and this subpopulation forms a vulnerable group with multiple problems. Fatal accidents with GBL are rarely reported, but non-fatal GHB (or GBL) overdoses frequently occur for which supportive treatment is needed. It is recommended to monitor the recreational use of GBL, the rate of GBL dependence treatment, and the improper trading of GB

Risks of 3D printing in consumer environments : Techniques, materials and products

alleen digitaal verschenenSteeds meer consumenten hebben thuis een 3D-printer staan. Ook kunnen consumenten producten laten printen bij gespecialiseerde bedrijven. Er worden vooral miniatuurfiguren en onderdelen van (technische) apparaten mee geprint, maar ook producten die in het dagelijks leven worden gebruikt, zoals telefoonhoesjes. Het RIVM heeft in opdracht van de Nederlandse Voedsel en Warenautoriteit (NVWA) onderzocht of er voor consumenten risico's kleven aan het gebruik van 3D-printers en de bijbehorende producten. Dat blijkt het geval te zijn, alleen is de omvang van het risico op basis van de beschikbare gegevens niet precies te duiden. Het risico is sterk afhankelijk van de mate waarin consumenten aan het materiaal of aan vrijgekomen stoffen worden blootgesteld. Bij 3D-printen worden meestal plastic draden omgesmolten en in laagjes tot het gewenste product gevormd. Technische risico's, bijvoorbeeld dat consumenten zich aan het warme apparaat of plastic branden, zijn door verantwoord gebruik gemakkelijk te beperken. Daarnaast ontstaan tijdens het printen dampen en kleine deeltjes die de gebruiker in kan ademen. Goed ventileren is belangrijk om dat te beperken. Verder kunnen consumenten aan chemische stoffen worden blootgesteld bij het gebruik van de geprinte producten. Dit kan via contact met de huid, zoals bij sieraden, en mond, bijvoorbeeld bij kinderspeelgoed of drinkbekers.A growing number of consumers have a 3D printer at home, or engage the services of specialized companies to print products. Frequently printed products include miniature figurines and components of technical and other equipment, as well as products used in daily life, such as phone cases. The Dutch National Institute for Public Health and the Environment (RIVM) was commissioned by the Dutch Food and Consumer Product Safety Authority (NVWA) to investigate whether the use of 3D printers and the associated products poses any risks to consumers. RIVM concluded that this is indeed the case, but that the severity of the risks involved cannot be accurately determined based on the available information. The risks depend to a large extent on consumers' exposure to specific materials or substances released during the printing process. Three-dimensional printing - also known as additive manufacturing - usually involves melting plastic wires and forming successive layers of material to create the required product. Technical risks (e.g. consumers suffering a burn from touching the hot printer or the hot plastic) can be easily mitigated through safe and responsible use. The printing process also produces fumes and small particles that can be inhaled by consumers. Adequate ventilation is important in order to reduce this risk. In addition, consumers may be exposed to chemical substances when using the printed products. Such exposure may occur through contact with the skin (e.g. in the case of jewellery) or mouth (e.g. children's toys and drinking cups).NVW

Levamisole-contaminated cocaine: a hairy affair

Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure

Risico's van 3D-printen in een consumentenomgeving : Technieken, materialen en producten

alleen digitaal verschene