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In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first-ever approval of a CRISPR-Cas9-based gene-editing cell therapy., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aquatic ecosystems are at risk of being impaired by various organic chemicals, however comprehensive large-scale evaluations of waterbodies' status and trends are rare. Here, surface water monitoring data, gathered as part of the EU Water Framework Directive and comprising the occurrence of 352 organic contaminants (>8.3 mil. measurements; 2001-2015; 8213 sites) in 31 European countries, was used to evaluate past and current environmental risks for three aquatic species groups: fish, invertebrates, plants. Monitoring quality indices were defined per country and found to improve over time. Relationships became apparent between countries' monitoring quality index and their success in detecting contaminants. Across the EU, contaminants were more frequently found in recent years. Overall, 35.7% (n = 17,484) of sites exceeded at least one acute regulatory threshold level (RTL) each year, and average risks significantly increased over time for fish (τ = 0.498, p = 0.01) and aquatic invertebrates (τ = 0.429, p = 0.03). This indicates an increased chemical pressure to Europe's waterbodies and overall large-scale threshold exceedances. Pesticides were identified as the main risk drivers (>85% of RTL exceedances) with aquatic invertebrates being most acutely at risk in Europe. Agricultural land-use was clearly identified as the primary spatial driver of the observed aquatic risks throughout European surface waters. Issues in monitoring data heterogeneity were highlighted and also followed by subsequent improvement recommendations, strengthening future environmental quality assessments. Overall, aquatic ecosystem integrity remains acutely at risk across Europe, signaling the demand for continued improvements., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The leaf-shredding crustacean Hyalella azteca, which is indigenous to Northern and Central America, is used to assess environmental risks associated with (metal-)contaminated sediments and to propose sediment quality standards also in Europe. Yet, it is unknown if H. azteca is protective for European crustacean shredders. We thus compared the sensitivity of H. azteca with that of the European species Asellus aquaticus and Gammarus fossarum towards copper- and cadmium-contaminated sediments (prepared according to OECD 218) under laboratory conditions employing mortality and leaf consumption as endpoints. H. azteca either reacted approximately fourfold more sensitive than the most tolerant tested species (as for cadmium) or its sensitivity was only 1.6 times lower than the highest sensitivity determined (as for copper), which should be covered by safety factors applied during risk assessments. Therefore, the results for the sediment type and the two heavy metals tested during the present study in combination with the existence of standardized testing protocols, their ease of culture, and short generation time, suggest H. azteca as suitable crustacean model shredder for assessing the toxicity of sediment-associated metals in Europe.

The decades-long agricultural use of insecticides resulted in frequent contamination of surface waters globally regularly posing high risks for the aquatic biodiversity. However, the concentration levels of individual insecticide compounds have by now not been compiled and reported using global scale data, hampering our knowledge on the insecticide exposure of aquatic ecosystems. Here, we specify measured insecticide concentrations (MICs, comprising in total 11,300 water and sediment concentrations taken from a previous publication) for 28 important insecticide compounds covering four major insecticide classes. Results show that organochlorine and organophosphate insecticides, which dominated the global insecticide market for decades, have been detected most often and at highest concentration levels in surface waters globally. In comparison, MICs of the more recent pyrethroids and neonicotinoids were less often reported and generally at lower concentrations as a result of their later market introduction and lower application rates. An online insecticide classification calculator (ICC; available at: https://static.magic.eco/icc/v1) is provided in order to enable the comparison and classification of prospective MICs with available global insecticide concentrations. Spatial analyses of existing data show that most MICs were reported for surface waters in North America, Asia and Europe, whereas highest concentration levels were detected in Africa, Asia and South America. An evaluation of water and sediment MICs showed that theoretical organic carbon-water partition coefficients (K OC ) determined in the laboratory overestimated K OC values based on actual field concentrations by up to a factor of more than 20, with highest deviations found for highly sorptive pyrethroids. Overall, the comprehensive compilation of insecticide field concentrations presented here is a valuable tool for the classification of future surface water monitoring results and serves as important input data for more field relevant toxicity testing approaches and pesticide exposure and risk assessment schemes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Invasive species are considered as one of the major threats for biodiversity worldwide. The Ponto-Caspian species Dikerogammarus villosus, for instance, spread throughout continental Europe and was recorded for the first time also within Lake Constance in 2003. Although D. villosus is a highly competitive species it was not capable of replacing the native Gammarus roeselii completely in this ecosystem, especially in the riparian zones of the highly agriculturally used island "Reichenau". As differences in pesticide sensitivity between both amphipod species may explain their distribution, the present study assessed the implication of the highly toxic pyrethroid lambda-cyhalothrin, which is authorized for application in the Lake Constance region, assuming the invasive species being more sensitive than the native one. However, both the feeding activity bioassays, which measured the leaf consumption over 7d (n=20), as well as the predation bioassay, which measured the predation rate upon Baetis nymphs in concert with the feeding activity on leaf material over 96 h (n=13), revealed an up to 5-fold higher tolerance of D. villosus towards lambda-cyhalothrin. These results suggest the investigated insecticide not being the trigger for the observed distribution pattern of both amphipod species. Hence, other factors like the diversity of habitat structures or the levels of ammonia may have facilitated the coexistence. Nevertheless, the present study uncovered a high leaf-shredding efficacy of the invasive species D. villosus suggesting that its role in the leaf decomposition process may have been underestimated in the past., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services., Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example., Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians., Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Ischaemic postconditioning (brief periods of ischaemia alternating with brief periods of reflow applied at the onset of reperfusion following sustained ischaemia) effectively reduces myocardial infarct size in all species tested so far, including humans. Ischaemic postconditioning is a simple and safe manoeuvre, but because reperfusion injury is initiated within minutes of reflow, postconditioning must be applied at the onset of reperfusion. The mechanisms of protection by postconditioning include: formation and release of several autacoids and cytokines; maintained acidosis during early reperfusion; activation of protein kinases; preservation of mitochondrial function, most strikingly the attenuation of opening of the mitochondrial permeability transition pore (MPTP). Exogenous recruitment of some of the identified signalling steps can induce cardioprotection when applied at the time of reperfusion in animal experiments, but more recently cardioprotection was also observed in a proof-of-concept clinical trial. Indeed, studies in patients with an acute myocardial infarction showed a reduction of infarct size and improved left ventricular function when they underwent ischaemic postconditioning or pharmacological inhibition of MPTP opening during interventional reperfusion. Further animal studies and large-scale human studies are needed to determine whether patients with different co-morbidities and co-medications respond equally to protection by postconditioning. Also, our understanding of the underlying mechanisms must be improved to develop new therapeutic strategies to be applied at reperfusion with the ultimate aim of limiting the burden of ischaemic heart disease and potentially providing protection for other organs at risk of reperfusion injury, such as brain and kidney.

Background: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region., Methods: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK)., Results: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome., Conclusion: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

The author analyzes results from a 1990 survey of family and social networks in the former Federal Republic of Germany. "Our project...focuses on the question as to what extent the changes in the observed demographic factors do affect and modify the system of the family with its various acts of assistance and support (financial help, emotional support, rendering of services)." The questionnaire used is provided, and survey methods are described., (excerpt)