Pharmaceuticals in the Environment: A hospital pharmacy's perspective. / El impacto ambiental de los medicamentos: una mirada desde la farmacia hospitalaria.

Drugs do not disappear once they have been excreted. In fact, 992 active principles have already been measured in the different environmental matrices. A recent study led by scientists from the University of York has studied the presence of drugs in the rivers of more than 100 different countries, showing that environmental contamination by pharmaceuticals is a global issue and that, concentrations found are frequently harmful to the environment. In this work, we have tried to briefly expose the problem of environmental contamination with medicines, but above all, we have tried to address the possible solutions, with a perspective from the field of hospital pharmacy. This is a very complex matter (a wicked problem), since it involves multiple stakeholders with different visions and interests regarding medicines. In order to find solutions, we will probably need to act at all steps of the drug's life cycle. Until now, health professionals have been part of the problem. It is time for us to be part of the solution.

[Translated article] Pharmaceuticals in the environment: A hospital pharmacy perspective.

Drugs do not disappear once they have been excreted. In fact, 992 active principles have already been measured in the different environmental matrices. A recent study led by scientists from the University of York has studied the presence of drugs in the rivers of more than 100 different countries, showing that environmental contamination by pharmaceuticals is a global issue and that, concentrations found are frequently harmful to the environment. In this work, we have tried to briefly expose the problem of environmental contamination with medicines, but above all, we have tried to address the possible solutions, with a perspective from the field of hospital pharmacy. This is a very complex matter (a wicked problem), since it involves multiple stakeholders with different visions and interests regarding medicines. In order to find solutions, we will probably need to act at all steps of the drug's life cycle. Until now, health professionals have been part of the problem. It is time for us to be part of the solution.

A Cross-Sectional Study to Assess the Knowledge of Pharmacy Students About Drug Pollution in Spain.

The presence of pharmaceuticals in the environment is an issue of growing concern. The European Commission adopted the "European Union Strategic Approach to Pharmaceuticals in the Environment", which focuses on actions to reduce the risk of pharmaceuticals in the environment, including how environmental aspects can become part of medical training programs. OBJECTIVE: Obtain data from pharmacy students about pharmaceutical pollution to provide information about the training needs that may help develop new actions related to the training and dissemination of this issue. METHODS: A total of 1614 pharmacy students from 5 Schools of Pharmacy in Spain completed a self-administered questionnaire consisting of 24 questions: 13 about knowledge, 8 related to attitude, and 3 to opinion. RESULTS: Around 75% of students reported that they did not know "One Health" or "emerging pollutant" concepts and around 88% declared that they did not know that diclofenac caused a catastrophic vulture decline in Asia. The importance of this topic and their attitude to acquiring new knowledge was evaluated higher than 8 points out of 10, while received training during their studies was a score of 2.8 points out of 10. CONCLUSION: The knowledge about key concepts was relatively poor. In fact, they judged training about pharmaceuticals in the environment during their pharmacy studies was very scarce. However, students consider drug pollution to be a very important issue and have a very good attitude toward acquiring knowledge about it.

Wastewater-based epidemiology methodology to investigate human exposure to bisphenol A, bisphenol F and bisphenol S.

Wastewater-based epidemiology (WBE) has become an invaluable tool for tracking the evolution of use or exposure of/to numerous substances. Bisphenols, commonly utilized in manufacturing plastic goods, have been categorized as endocrine disrupting chemicals, underscoring the critical need for real-time data on their local-level exposure to safeguard public health. In this study, we have developed a novel analytical method and WBE framework for the assessment of population-level exposure to bisphenol A (BPA) and its most prominent substitutes, bisphenols F and S (BPF and BPS), through the determination their Phase II metabolites in wastewater by WBE. Stability and exclusivity tests denoted that glucuronides are not stable in sewage, whereas sulfate metabolites are good biomarkers. Therefore, a solid-phase extraction followed by liquid chromatography-tandem mass spectrometry method was developed for the bisphenols' monosulfates and BPA bissulfate. The analytical method was validated with three different wastewater matrices, providing trueness (as recovery) in the 79-112 % range with relative standard deviations < 12 %, and method quantification limits below 2 ng L-1 for monosulfates, but higher (35 ng L-1) for BPA bissulfate. Subsequently, the method was applied to 24h-composite raw wastewater samples collected over a week in 4 different locations in Spain and Portugal. BPA bissulfate was not detected, but the three monosulfate metabolites of each bisphenol were positively detected in the samples, being the metabolite of BPA the most prevalent, followed by those of BPF and BPS. Community-wide BPA intake was then estimated to be higher than the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10-4 µg kg-1day-1 in all locations. In the case of BPF and BPS, there is not enough metabolism data or even established limit, but they would also surpass safe levels in several locations if a similar metabolism and TDI would be assumed. This innovative method could be used to a larger set of wastewater-treatment plants as an early-warning approach on human exposure to bisphenols.

Acetazolamide-induced pulmonary oedema: A disproportionality analysis from the EudraVigilance database.

To our knowledge, no prior study has analysed a possible association between acetazolamide and pulmonary oedema. The aim of this study was to use data from the EudraVigilance to detect a safety signal for acetazolamide-induced pulmonary oedema. We performed a disproportionality analysis (case-noncase method), calculating reporting odds ratios (RORs) up to 22 February 2024. Among 11 684 208 spontaneous cases of adverse reactions registered in EudraVigilance, 38 275 were pulmonary oedemas. Acetazolamide was involved in 31 cases. In more than half of those cases, the patients received a single dose of acetazolamide after undergoing cataract surgery: latency was 10-90 min. Remarkably, there were five cases of positive rechallenge and six cases resulted in death. The ROR for acetazolamide was 3.63 (95% CI 2.55-5.17). Disproportionality was also observed in VigiBase®: ROR 4.44 (95% CI 3.34-5.90). Our study confirms a signal that suggests a risk of serious pulmonary oedema associated with acetazolamide.

A proposal to reduce the amount of permethrin entering wastewater resultant from topical use to treat scabies.

The incidence of scabies is rising in the last years. Subsequently, the use of pharmaceuticals to treat the disease has also increased. Treatment with topical permethrin is usually recommended as a first line agent. This substance is also an aquatic contaminant that is toxic for many non-target organisms, and has been included as a priority substance in the recently published proposal of the European Water Framework Directive. Current guidelines neglect the potential environmental impact of this drug, recommending that the cream should be applied head to toe and "washed off after 8-12 h". Recently, a wiping procedure before hand washing after application of the topical treatment resulted in a 66 % reduction of the amount of diclofenac released in wastewater. The authors suggested that this method could be explored for other topical treatments. In the case of scabiosis, a protocol implicating the whole body needs to be designed. The absorption of topical permethrin is low. Considering the growing incidence of scabies, the amount of the pyrethroid reaching the environment may also be increasing. Therefore, we believe that applying the wiping procedure to the case of topical permethrin deserves consideration. Other measures to minimize the amount of permethrin residues reaching wastewater by washing clothes and bed linen such as wearing single-use pijamas should also be explored. In conclusion, we need to apply a One Health approach in the treatment with scabies, without neglecting the environmental impact of pharmaceuticals. It is not rational to forget drugs once they go down the drain.

Pharmaceutical residues in stranded dolphins in the Bay of Biscay.

There is a growing concern about the presence of pharmaceuticals on the aquatic environment, while the marine environment has been much less investigated than in freshwater. Marine mammals are suitable sentinel species of the marine environment because they often feed at high trophic levels, have unique fat stores and long lifespan. Some small delphinids in particular serve as excellent sentinel species for contamination in the marine environment worldwide. To the best of our knowledge, no pharmaceuticals have been detected or reported in dolphins so far. In the present study, muscle, liver and blubber samples from three common dolphins (Delphinus delphis) and seven striped dolphins (Stenella coeruleoalba) stranded along the Basque Coast (northern Spain) were collected. A total of 95 pharmaceuticals based on detectability and predicted ability to bioaccumulate in fish were included in the liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. At least one pharmaceutical was found in 70 % of the individuals. Only three of the 95 monitored pharmaceuticals were detected in dolphin's tissues. Very low concentrations (<1 ng/g) of orphenadrine and pizotifen were found in liver and promethazine in blubber. Herein, the gap in the knowledge regarding the study organisms and marine environments with respect to pharmaceutical pollution, which demands further research to understand if pharmaceuticals are a threat for these apex predators, is highlighted and discussed.

Occurrence and ecological risk assessment of organic UV filters in coastal waters of the Iberian Peninsula.

This study aimed to assess the presence of 21 UVFs and metabolites in coastal regions of the Iberian Peninsula, to evaluate their environmental risk, and identify possible influential factors affecting their measured concentrations. Sampling was carried out in spring and summer to assess possible seasonal variations. UVFs were detected in 43 of the 46 sampling sites. Only 5 were found above LOD: BP4, OC, BP3 and metabolites BP1 and BP8. Samples collected in Mar Menor had the greatest variety of compounds per sample and the highest cumulative concentrations. The risk was characterized using Risk Quotients (RQ). BP1 showed a Low environmental Risk in 2 sites while for OC the RQ indicated a Moderate Risk in 22 points. The variables that contribute most to the variation are population density, sampling season, whether it was an open bay or not, and level of urbanization. The presence of WWTPs had a lower influence.

Pharmaceuticals in hospital wastewaters: an analysis of the UBA's pharmaceutical database.

The presence of pharmaceuticals in hospital wastewaters (HWW) has been a focus of interest for researchers in the last decades. Certain therapeutic classes, such as X-ray contrast media, broad-spectrum antimicrobials and cytotoxics among others, are mainly used in hospitals-health care facilities. This study is focused on available studies monitoring the presence of pharmaceuticals in HWW around the world. To that end, the last available version (v3. 2021) of the "Pharmaceuticals in the Environment" database published by the Federal German Environment Agency (Umweltbundesamt) has been used. Almost half of all studies included (107) have been conducted in Europe. Pharmaceuticals have been monitored in HWW in 38 different countries across all five continents. The country with the greatest number of studies is Brazil (11), followed by Spain (8), China (7), and France (6). Our analysis revealed that 271 different pharmaceuticals have been detected at least once in HWW. The five drugs with more studies showing a positive detection are ciprofloxacin (38), sulfamethoxazole (36), diclofenac (34), ibuprofen (29), and trimethoprim (27). A total of 47 out of 271 drugs are considered in the NIOSH "Hazardous drug" list. However, monitoring data for some widely used drugs in hospital settings such as muscle relaxants, anesthetics, and antidotes is lacking. In conclusion, this study provides the first large-scale metadata analysis for the pharmaceuticals in HWW worldwide.

Knowledge and attitude about drug pollution in pharmacy students: A questionnaire-based cross sectional study.

INTRODUCTION: The environmental impact of drugs or pharmaceuticals is an issue of growing concern. Healthcare professionals, and pharmacists in particular, are used to managing medicines, yet aspects about drug pollution are generally neglected in schools of pharmacy worldwide. Formation in this issue is essential to tackle the problem. In this study, we aimed to find out the degree of knowledge about the problem of pharmaceuticals in the environment and the attitude about the matter of pharmacy students at the University of the Basque Country. METHODS: We conducted a pilot study (186 students) using an online questionnaire available in two languages (Basque and Spanish). The attitude scale was validated for Spanish. To improve participation, a combination of indirect and direct recruitment was applied in the final study. RESULTS: Four hundred eighty-seven students participated in the final study (response rate: 65.8%). The final questionnaire contained a total of 25 questions: 13 (knowledge), eight (attitude), and three (opinion). The results showed that knowledge can be considered relatively poor, whereas attitude was generally positive, and students considered drug pollution to be a relevant issue in general and in pharmacy practice. CONCLUSIONS: We believe there is an urgent need to include aspects about pharmaceuticals in the environment in pharmacy studies worldwide.

Analysis of heat stroke and heat exhaustion cases in EudraVigilance pharmacovigilance database.

BACKGROUND: The frequency and intensity of heat waves have increased and will keep increasing. This meteorological phenomenon, which is considered one of the most dangerous, can affect the entire population, but certain populations are at greater risk. Concretely, elderly people are more prompt to suffer from chronic diseases and therefore to be on medication that can interact with the different temperature-regulating systems of the body. So far, there are no published studies that have analyzed pharmacovigilance databases to characterize the association between specific pharmaceuticals and heat-related adverse reactions. OBJECTIVE: Therefore, in this study, we aimed to investigate the reported cases of heat exhaustion or heat stroke, associated with any drug notified to the European pharmacovigilance database (EudraVigilance). METHOD: The Basque Country Pharmacovigilance Unit selected spontaneous reports recorded in EudraVigilance from January 1, 1995, to January 10, 2022. "Heat Stroke" and "Heat Exhaustion" preferred terms were selected. Non-cases, used as controls, were all the other adverse drug reaction reports recorded in EudraVigilance for the same time period. RESULTS: In total, 469 cases were obtained. Mean age: 49.74 ± 8 years, 62.5% were male, and the majority (94.7%) were considered serious by EU criteria. Fifty-one active substances fulfilled the criteria to generate a signal of disproportionate reporting. CONCLUSIONS: The majority of implicated drugs belong to therapeutic groups that are already mentioned in different heat-illness prevention plans. But we also show that drugs aimed to treat multiple sclerosis and several cytokines were also associated with heat-related adverse effects.

Correlation between SARS-CoV-2 RNA concentration in wastewater and COVID-19 cases in community: A systematic review and meta-analysis.

Wastewater-based epidemiology (WBE) has been considered as a promising approach for population-wide surveillance of coronavirus disease 2019 (COVID-19). Many studies have successfully quantified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentration in wastewater (CRNA). However, the correlation between the CRNA and the COVID-19 clinically confirmed cases in the corresponding wastewater catchments varies and the impacts of environmental and other factors remain unclear. A systematic review and meta-analysis were conducted to identify the correlation between CRNA and various types of clinically confirmed case numbers, including prevalence and incidence rates. The impacts of environmental factors, WBE sampling design, and epidemiological conditions on the correlation were assessed for the same datasets. The systematic review identified 133 correlation coefficients, ranging from -0.38 to 0.99. The correlation between CRNA and new cases (either daily new, weekly new, or future cases) was stronger than that of active cases and cumulative cases. These correlation coefficients were potentially affected by environmental and epidemiological conditions and WBE sampling design. Larger variations of air temperature and clinical testing coverage, and the increase of catchment size showed strong negative impacts on the correlation between CRNA and COVID-19 case numbers. Interestingly, the sampling technique had negligible impact although increasing the sampling frequency improved the correlation. These findings highlight the importance of viral shedding dynamics, in-sewer decay, WBE sampling design and clinical testing on the accurate back-estimation of COVID-19 case numbers through the WBE approach.