Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

peer reviewedDespite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG

Impact of anti-inflammatories, beta-blockers and antibiotics on leaf litter breakdown in freshwaters

Pharmaceuticals are now recognised as important pollutants in freshwater systems but a shortcoming of effects studies is that they have focused on structural endpoints and impacts on ecosystem functioning are poorly understood. The decomposition of organic matter is an important functional process in aquatic systems and it is known that this can be impacted by the presence of pollutants. Previous studies on leaf litter breakdown have only considered the effects of antibiotics and not other groups of drugs though. The current study investigated the effects of anti-inflammatories, a beta-blocker and an antibiotic on microbially mediated breakdown of leaf litter in the laboratory, colonisation of leaf packs by benthic macroinvertebrates when placed in a stream and shredding of leaf litter by these organisms. Furthermore, the effects of single compounds relative to their mixture were assessed. It was found that exposure of leaf litter to the study compounds did not influence its breakdown by microbes in the laboratory or macroinvertebrates in a stream. Exposure of leaf litter to pharmaceuticals also had no effect on its colonisation by macroinvertebrates in this study. Many unknowns remain, however, and further studies of the effects of pharmaceuticals on structural and functional endpoints are needed to aid aquatic conservation

Temporal variability of antibiotics fluxes in wastewater and contribution from hospitals.

Significant quantities of antibiotics are used in all parts of the globe to treat diseases with bacterial origins. After ingestion, antibiotics are excreted by the patient and transmitted in due course to the aquatic environment. This study examined temporal fluctuations (monthly time scale) in antibiotic sources (ambulatory sales and data from a hospital dispensary) for Lausanne, Switzerland. Source variability (i.e., antibiotic consumption, monthly data for 2006-2010) were examined in detail for nine antibiotics--azithromycin, ciprofloxacin, clarithromycin, clindamycin, metronidazole, norfloxacin, ofloxacin, sulfamethoxazole and trimethoprim, from which two main conclusions were reached. First, some substances--azithromycin, clarithromycin, ciprofloxacin--displayed high seasonality in their consumption, with the winter peak being up to three times higher than the summer minimum. This seasonality in consumption resulted in seasonality in Predicted Environmental Concentrations (PECs). In addition, the seasonality in PECs was also influenced by that in the base wastewater flow. Second, the contribution of hospitals to the total load of antibiotics reaching the Lausanne Wastewater Treatment Plant (WTP) fluctuated markedly on a monthly time scale, but with no seasonal pattern detected. That is, there was no connection between fluctuations in ambulatory and hospital consumption for the substances investigated

Comparative ecotoxicological hazard assessment of beta-blockers and their human metabolites using a mode-of-action-based test battery and a QSAR approach

We analyzed nontarget effects of the β-blockers propranolol, metoprolol, and atenolol with a screening test battery encompassing nonspecific, receptor-mediated, and reactive modes of toxic action. All β-blockers were baseline toxicants and showed no specific effects on energy transduction nor endocrine activity in the yeast estrogen and androgen screen, and no reactive toxicity toward proteins and DNA. However, in a phytotoxicity assay based on the inhibition of the photosynthesis efficiency in green algae, all β-blockers were 10 times more toxic than their modeled baseline toxicity. Baseline- and phytotoxicity effects increased with hydrophobicity. The β-blockers showed concentration addition in mixture experiments, indicating a mutual specific nontarget effect on algae. Using literature data and quantitative structure−activity relationships (QSAR), we modeled the total toxic potential of mixtures of the β-blockers and their associated human metabolites for the phytotoxicity endpoint with two scenarios. The realistic scenario (I) assumes that the metabolites lose their specific activity and act as baseline toxicants. In the worst-case scenario (II) the metabolites exhibit the same specific mode of action as their parent drug. For scenario (II), metabolism hardly affected the overall toxicity of atenolol and metoprolol, whereas propranolol's hazard potential decreased significantly. In scenario (I), metabolism reduced the apparent EC50 of the mixture of parent drug and metabolite even further. The proposed method is a simple approach to initial hazard assessment of pharmaceuticals and can guide higher tier testing. It can be applied to other classes of pollutants, e.g., biocides, as well as to environmental transformation products of pollutants