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Hydrological droughts are expected to increase in frequency and severity in many regions due to climate change. Over the last two decades, several droughts occurred in Europe, including the 2018-drought, which showed major adverse impacts for nature and different sectoral uses (e.g. irrigation, drinking water). While drought impacts on water quantity are well studied, little understanding exists on the impacts on water quality, particularly regarding pharmaceutical concentrations in surface waters. This study investigates the impact of the 2018-drought on concentrations of four selected pharmaceuticals (carbamazepine, sulfamethoxazole, diclofenac and metoprolol) in surface waters in Europe, with a major focus on the Elbe and Rhine rivers. Monitoring data were analysed for the period of 2010-2020 to estimate the spatiotemporal patterns of pharmaceuticals and assess the concentration responses in rivers during the 2018-drought compared to reference years. Our results indicate an overall deterioration in water quality, which can be attributed to the extremely low flow and higher water temperatures (∼ + 1.5 °C and + 2.0 °C in Elbe and Rhine, respectively) during the 2018-drought. Our results show an increase in the concentrations of carbamazepine, sulfamethoxazole, and metoprolol, but reduced concentrations of diclofenac during the 2018-drought. Significant increases in carbamazepine concentrations (+45 %) were observed at 3/6 monitoring stations in the upstream part of the Elbe, which was mainly attributed to less dilution of chemical loads from wastewater treatment plants under drought conditions. However, reduced diclofenac concentrations could be attributed to increased degradation processes under higher water temperatures (R 2  = 0.60). Moreover, the rainfed-dominated Elbe exhibited more severe water quality deterioration than the snowmelt-dominated Rhine river, as the Elbe's reduction in dilution capacity was larger. Our findings highlight the need to account for the impacts of climate change and associated increases in droughts in water quality management plans, to improve the provision of water of good quality for ecosystems and sectoral needs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Contaminants of emerging concern (CEC) are a focus in marine protection. Several CECs are released with wastewater effluents to coastal environments and their offshore occurrence has been recently documented. Routine monitoring is key for implementing marine protection acts, however infrastructural, financial, and technical limitations hinder this task along broad spatial transects. Here we show the efficacy of a new infrastructure enabling unmanned sampling of surface water from ships of opportunity in providing reliable and cost-effective routine monitoring of CECs along a Europe-Arctic transect. The distribution and long-range transport of several pharmaceuticals and personal care products, artificial food additives, and stimulants were assessed. Validation of operations through strict procedural and analytical quality criteria is presented. A framework to estimate a compound-specific spatial range (SR) index of marine long-range transport based on monitoring results and information on source spatial distribution, is introduced. Estimated SR values ranged 50–350 km depending on compound, yielding a ranking of long-range transport potential which reflected expectations based on degradation half-lives. SR values were used to calculate prior maps of detection probability that can be used to plan future routine monitoring in the region. [Display omitted] • Marine CECs analyzed through unmanned sampling from ships of opportunity. • Several CECs were successfully detected along a Europe-Arctic transect. • A Marine long-range transport index empirically determined for tracer compounds. • Prior maps of detection probability presented to inform future monitoring. [ABSTRACT FROM AUTHOR]

Abstract: A human health risk assessment was carried out for environmental exposures to carbamazepine (CBZ) and its major human metabolites, carbamazepine diol (CBZ-DiOH) and carbamazepine N-glucuronide (CBZ-N-Glu). Carbamazepine is an active pharmaceutical ingredient (API) used worldwide as a medicine for treating epileptic seizures and trigeminal neuralgia. Carbamazepine tends to be detected in surface water more frequently, and at relatively higher concentrations, than most other APIs. Predicted no effect levels (PNECs) for CBZ and its major human metabolites were developed for surface waters to be protective of human health from environmental exposures from drinking water and fish consumption. These PNECs were compared to both measured (MEC) and predicted (PEC) environmental concentrations for North America and Europe. PECs were calculated using the geo-referenced models PhATE™ for North America and GREAT-ER for Europe. The combined PNEC for drinking water and fish consumption for CBZ is 226,000ng/L. Ninetieth percentile MECs ranged from 150 to 220ng/L, while 90th percentile PECs ranged from 333 to 658ng/L. Calculated margins of safety (MOS) therefore range from 340 to 1500. MOS for the major metabolites are significantly higher. This assessment indicates that CBZ and its major metabolites have high MOS (≫1) and thus should have no appreciable risk to human health through environmental exposures based on available human data. [Copyright &y& Elsevier]

Pharmaceuticals released into aquatic systems are expected to sorb to sediments to varying degrees. Their sorption is likely to influence their fate and, ultimately, the risk they pose to aquatic organisms. This has led to the European Medicines Agency requiring an assessment of affinity to solids, using batch sorption methods, for the environmental risk assessment (ERA) of new human medicines. However, a large body of data is generated before pharmaceuticals are released onto the market, including their extent of distribution throughout the human body, measured by the volume of distribution (VD). In the present study, batch sorption experiments were undertaken using 12 different soils and sediments to determine whether VD was a good indicator of experimental Kd values for 21 pharmaceuticals. The r² values obtained from the regressions ranged from 0.39 to 0.76 (with a median value of 0.5) and all regressions were found to be significant. The use of this more comprehensive set of soils and sediments was consistent with previous studies comparing VD and Kd, despite the Kd values of the selected pharmaceuticals varying greatly between soils. The relationship between Kd and VD was greatly improved when zwitterionic antibiotics and carbamazepine were not included, possibly due to complex sorption or pharmacokinetic behavior. There are likely to be a number of factors affecting the sorption of pharmaceuticals that cannot be explained by VD. However, further work may elucidate how these factors can be accounted for, enabling VD to be effectively used to facilitate the ERA of human pharmaceuticals with already available information. [ABSTRACT FROM AUTHOR]

Abstract: This study provides the first EU-wide reconnaissance of the occurrence of polar organic persistent pollutants in European river waters. More than 100 individual water samples from over 100 European rivers from 27 European Countries were analysed for 35 selected compounds, comprising pharmaceuticals, pesticides, PFOS, PFOA, benzotriazoles, hormones, and endocrine disrupters. Around 40 laboratories participated in this sampling exercise. The most frequently and at the highest concentration levels detected compounds were benzotriazole, caffeine, carbamazepine, tolyltriazole, and nonylphenoxy acetic acid (NPE1C). Only about 10% of the river water samples analysed could be classified as “very clean” in terms of chemical pollution. The rivers responsible for the major aqueous emissions of PFOS and PFOA from the European Continent could be identified. For the target compounds chosen, we are proposing “indicative warning levels” in surface waters, which are (for most compounds) close to the 90th percentile of all water samples analysed. [Copyright &y& Elsevier]

Prescription and nonprescription drugs have been detected in rivers and streams in Europe and the United States. Sewage treatment plants (STPs) are an important source of these contaminants, but few data exist on the spatial distribution of drugs in surface waters near STPs. Samples of surface water were collected in the summer and fall of 2000 at open-water sites in the lower Great Lakes (Lake Ontario and Lake Erie), at sites near the two STPs for the city of Windsor (ON, Canada), and at sites in Hamilton Harbour (ON, Canada), an embayment of western Lake Ontario that receives discharges from several STPs. In a follow-up study in the summer of 2002, samples of surface water and final effluent from adjacent STPs were collected from sites in Hamilton Harbour and Windsor. In addition, surface water and STP effluent samples were collected in Peterborough (ON, Canada). All samples of surface water and STP effluents were analyzed for selected acidic and neutral drugs. In the survey of Hamilton Harbour and Windsor conducted in 2000, acidic drugs and the antiepileptic drug carbamazepine were detected at ng/L concentrations at sites that were up to 500 m away from the STP, but the hydrological conditions of the receiving waters strongly influenced the spatial distribution of these compounds. Drugs were not detected at open-water locations in western Lake Erie or in the Niagara River near the municipality of Niagara-on-the-Lake (ON, Canada). However, clofibric acid, ketoprofen, fenoprofen, and carbamazepine were detected in samples collected in the summer of 2000 at sites in Lake Ontario and at a site in the Niagara River (Fort Erie, ON, Canada) that were relatively remote from STP discharges. Follow-up studies in the summer of 2002 indicated that concentrations of acidic and neutral drugs in surface waters near the point of sewage discharge into the Little River (ON, Canada) STP were approximately equal to the concentrations in the final effluent from the STP. Caffeine and cotinine, a metabolite of nicotine, were generally present in STP effluents and surface waters contaminated by drugs. The antidepressant fluoxetine and the antibiotic trimethoprom were also detected in most STP effluents and some surface water samples. For the first time, the lipid regulating drug atorvastatin was detected in samples of STP effluent and surface water. [ABSTRACT FROM AUTHOR]

In Europe, emerging organic compounds (EOCs) in groundwater is a growing research area. Prioritisation for monitoring EOCs in Europe was formalised in 2019 through the development of the first voluntary groundwater watch list (GWWL). Despite this, groundwater occurrence data in the peer reviewed literature for Europe has not been reviewed to date. Questions surrounding the effect, toxicity, movement in the subsurface and unsaturated zone make the process of regulating EOC use difficult. The aim in Europe is to develop a unified strategy for the classification, and prioritisation of EOCs to be monitored in groundwater. This paper compiles evidence from the recent published studies from across Europe, since 2012, when the last major literature global review of EOCs in groundwater took place. A total of 39 studies were identified for review based on specific selection criteria (geography, publication date, sample size>10, inclusion of EOCs data). Data on specific compounds, and associated meta-data, are compiled and reviewed. The two most frequently detected EOCs, carbamazepine and caffeine, occurred in groundwater at concentrations of up to 2.3 and 14.8 μg/L, respectively. The most frequently reported category of compounds were 'Pharmaceuticals'; a highly studied group with 135 compounds identified within 31 of the 39 studies. In Europe, the majority of reviewed studies (23) were at a regional scale, looking specifically at EOCs in a specific city or aquifer. The use of analytical methods is not uniform across Europe, and this inevitably influences the current assessment of EOCs in groundwater. A correlation between the number of compounds analysed for, and the number detected in groundwater highlights the need for further studies, especially larger-scale studies throughout Europe. For the development of EU and national regulation, further work is required to understand the occurrence and impacts of EOCs in groundwater throughout Europe and elsewhere. Image 1 • 39 studies reviewed to assess occurrence of EOCs in European groundwater. • Most reported category 'Pharmaceuticals'. • Maximum carbamazepine and caffeine concentrations 2.3 μg/L, and 14.8 μg/L respectively. • Strong correlation between number of compounds screened for and detections. • Standardised reporting needed to assess the current compounds of emerging concern. Assessing the occurrence of emerging organic compounds in European groundwater; implications for environmental exposure. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy, safety and tolerability of eslicarbazepine acetate (ESL) in patients transitioning from carbamazepine or oxcarbazepine to ESL in clinical practice, by analysing data from the Euro-Esli study., Methods: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness assessments included responder rate (≥50 % seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit), assessed after 3, 6 and 12 months of ESL treatment, and at the last visit. Safety and tolerability were assessed throughout follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Data were analysed for cohorts of patients who transitioned from carbamazepine and oxcarbazepine to ESL either due to lack of efficacy or poor tolerability., Results: Euro-Esli included 2058 patients, of whom 233 (11.3 %) transitioned from carbamazepine to ESL and 134 (6.5 %) transitioned from oxcarbazepine to ESL. After 12 months of ESL treatment, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n = 163) were 70.0 % and 30.9 %, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n = 90) were 57.1 % and 25.0 %, respectively. Among patients who transitioned from carbamazepine and oxcarbazepine to ESL due to poor tolerability (n = 64 and n = 61, respectively), 26.6 % and 39.5 % experienced AEs, and 8.3 % and 6.8 % discontinued ESL due to AEs, respectively., Conclusion: ESL was efficacious and generally well tolerated in patients transitioning from carbamazepine or oxcarbazepine in clinical practice due to inadequate seizure control or intolerable AEs with these agents., Competing Interests: Declaration of Competing Interest RR is a consultant for Eisai, Bial, UCB, GlaxoSmithKline and Shire, and receives grant and research support from Bial, Eisai, and UCB. JP has participated in clinical trials for Eisai, UCB, and Bial; received research grants from Eisai, Medtronic, UCB, and Cyberonics; received speaker honoraria from Cyberonics, Eisai, Medtronic, Orion Pharma, and UCB; received support for travel to congresses from Cyberonics, Eisai, Medtronic, and UCB; and participated in advisory boards for Cyberonics, Eisai, Medtronic, UCB, and Pfizer. GA has no conflicts of interest. RM is a current employee of Eisai Europe Ltd. VV has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai, UCB Pharma, Bial, Pfizer, GSK, Esteve, Novartis and GW Pharma., (Copyright © 2019. Published by Elsevier Ltd.)

The article discusses a study by J. Janszky and colleagues on patient recruitment in antiepileptic drug (AED) randomized controlled trial (RCT) design published in a 2010 issue of "Epilepsia." It mentions that AED RCTs are criticized for their inclination towards the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. The study emphasizes one shortcoming of AED RCTs, the failure to incorporate progress in evidence-based epilepsy management into the design of the study due to the neglect of eligibility for epilepsy surgery.

The article presents guidelines on the diagnosis and treatment of trigeminal neuralgia. It presents recommendations made by the American Academy of Neurology (AAN) and European Federation of Neurological Societies (EFNS) after reviewing literature related to the disease. Both organizations recognize the possible effectiveness, ineffectiveness or harmfulness of routine neuroimaging in determining a structural cause of the disease in up to 15% of such patients. AAN and EFNS acknowledge the efficacy of carbamazepine in controlling pain among such patients.

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed the management of trigeminal neuralgia in primary care and the association between long-term opioid use and osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy., Methods: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥ 60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency., Results: Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0)., Significance: In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)