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.

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.

Multidisciplinary Collaboration for the Optimization of Antibiotic Prescription: Analysis of Clinical Cases of Pneumonia between Emergency, Internal Medicine, and Pharmacy Services.

BACKGROUND: Pneumonia is a lung parenchyma acute infection usually treated with antibiotics. Increasing bacterial resistances force the review and control of antibiotic use criteria in different health departments. OBJECTIVE: Evaluate the adequacy of antibiotic treatment in community-acquired pneumonia in patients initially attended at the emergency department and then admitted to the internal medicine service of the Alto Deba Hospital-Osakidetza Basque Country Health Service (Spain). METHODS: Observational, retrospective study, based on the review of medical records of patients with community-acquired pneumonia attended at the hospital between January and May 2021. The review was made considering the following items: antimicrobial treatment indication, choice of antibiotic, time of administration of the first dose, adequacy of the de-escalation-sequential therapy, duration of treatment, monitoring of efficacy and adverse effects, and registry in the medical records. The review was made by the research team (professionals from the emergency department, internal medicine, and pharmacy services). RESULTS: Fifty-five medical records were reviewed. The adequacy of the treatments showed that antibiotic indication, time of administration of the first dose, and monitoring of efficacy and adverse effects were the items with the greatest agreement between the three departments. This was not the case with the choice of antibiotic, de-escalation/sequential therapy, duration of treatment, and registration in the medical record, which have been widely discussed. The choice of antibiotic was optimal in 63.64% and might have been better in 25.45%. De-escalation/oral sequencing might have been better in 50.91%. The treatment duration was optimal in 45.45% of the patients and excessive in 45.45%. DISCUSSION: The team agreed to disseminate these data among the hospital professionals and to propose audits and feedback through an antibiotic stewardship program. Besides this, implementing the local guideline and defining stability criteria to apply sequential therapy/de-escalation was considered essential.

Environmental pollution with psychiatric drugs.

Among all contaminants of emerging interest, drugs are the ones that give rise to the greatest concern. Any of the multiple stages of the drug's life cycle (production, consumption and waste management) is a possible entry point to the different environmental matrices. Psychiatric drugs have received special attention because of two reasons. First, their use is increasing. Second, many of them act on phylogenetically highly conserved neuroendocrine systems, so they have the potential to affect many non-target organisms. Currently, wastewater is considered the most important source of drugs to the environment. Furthermore, the currently available wastewater treatment plants are not specifically prepared to remove drugs, so they reach practically all environmental matrices, even tap water. As drugs are designed to produce pharmacological effects at low concentrations, they are capable of producing ecotoxicological effects on microorganisms, flora and fauna, even on human health. It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain. Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties, a large number of stakeholders with different values and interests, and enormous complexity. Possible solutions consist on acting at source, using medicines more rationally, eco-prescribing or prescribing greener drugs, designing pharmaceuticals that are more readily biodegraded, educating both health professionals and citizens, and improving coordination and collaboration between environmental and healthcare sciences. Besides, end of pipe measures like improving or developing new purification systems (biological, physical, chemical, combination) that eliminate these residues efficiently and at a sustainable cost should be a priority. Here, we describe and discuss the main aspects of drug pollution, highlighting the specific issues of psychiatric drugs.

Environmental contamination by pet pharmaceuticals: A hidden problem.

As the environmental risks of companion animal pharmaceuticals has been assumed to be low, currently, no data on the fate, behaviour or effect is required by the European Medicines Agency. This is in sharp contrast with what happens in farming animals, where ecotoxicological data is a pivotal part on the benefit-risk assessment for the marketing authorization of a new veterinary drug. Recently, concern about the environmental impacts from the indiscriminate prophylactic use of antiparasitic drugs in pets has arisen. Considering the notable increase of companion animals in Europe since 2010, our impression is that, effects and potential deleterious consequences of other therapeutic classes such as antimicrobials and psychotropic drugs are probably underrated. We believe that pets, as animals, should not be excluded from One Health's philosophy, and that authorities should incorporate environmental aspects in the benefit-risk assessment for drugs used in companion animals as well.

Ivermectin & COVID-19: Let's keep a One Health perspective.

Despite uncertainty about its clinical benefit, ivermectin has been used for COVID 19, even in prophylaxis. The European Medicines Agency (EMA) has advised against its use for the prevention or treatment of COVID-19 outside randomised clinical trials. Although the potential negative environmental effects of ivermectin have been widely recognised when used in veterinary medicine, scarce attention has been devoted to the potential ecotoxicological impact of human use. We believe is time to include One Health's philosophy in our daily practice. In the specific case of ivermectin & COVID 19, environmental aspects should also be on the table.

Pharmacotherapeutic management of Parkinson's disease inpatients: how about asking hospital pharmacists?

INTRODUCTION: Parkinson's disease (PD) is considered to be the fastest growing neurological disorder in the world. Patients with PD are hospitalised more frequently, have longer admissions and experience more complications during hospitalisation than age-matched control groups. The incorrect timing of levodopa administration and prescription of contraindicated antidopaminergic drugs are the most important risk factors for motor function deterioration during hospital admission, and have been associated with longer hospital stays and even increased mortality. Despite their crucial role in pharmacotherapy, little attention has been paid to the perspective of hospital pharmacists. The objective of this study was to identify key issues in the pharmacotherapeutic management of inpatients with PD by the implementation of a national Spanish survey specifically designed to analyse the perspective of hospital pharmacists. METHODS: An internet-based questionnaire covering the following areas was designed: hospital and participant characteristics, drug formulary, medication compliance and reconciliation, protocols and contraindicated drugs and areas for improvement. RESULTS: A total of 76 pharmacists from 59 hospitals answered the survey. Some weaknesses were identified in the availability of drugs: (1) pharmacy services closed at certain times (86.4%); (2) low variety of antiparkinsonian drugs (18.4% store >21 different drugs); (3) delay in antiparkinsonian drug administration if unavailable (>12 hours in 39.5% of cases); (4) lack of flexibility in administration times; (5) low availability of transdermal rotigotine and subcutaneous apomorphine (<50%). The participants ranked highly the designing of specific protocols for patients with PD and implementation of concrete actions to optimise PD inpatient pharmacotherapy. CONCLUSIONS: The participants detected some improvement opportunities and proposed realistic and applicable recommendations and strategies aiming to enhance the safety of patients with PD. Protocols for antiparkinsonian drug interchange, administration timing and nil by mouth status, medication reconciliation, and handling nausea/vomiting or psychotic symptoms are considered the main improvement areas.

Aripiprazole and impulse control disorders: higher risk with the intramuscular depot formulation?

Dopamine agonists have been associated with an increased risk of developing impulse control disorders (ICDs). The US Food and Drug Administration (FDA) issued a safety warning in 2016 of a possible association between ICDs and aripiprazole. Recently, one large epidemiological study has confirmed this risk. In the present study, we aim to determine whether the safety signal of ICDs associated with aripiprazole detected by the FDA is replicated in the European pharmacovigilance database (EudraVigilance). We searched for all suspected spontaneous cases of ICDs associated with aripiprazole in EudraVigilance up to 23 February 2017. To assess the association between ICD cases and each dopamine agonist drug, we calculated the proportional reporting ratios (PRRs). Among 4 905 110 events of all types recorded in EudraVigilance, we found 160 cases of ICDs associated with aripiprazole. Aripiprazole fulfilled the criteria to generate a safety signal; PRR (95% confidence interval): 16.39 (13.97-19.24). Notably, the association seemed the strongest for the depot formulation of aripiprazole; PRR (95% confidence interval): 27.13 (17.22-42.75). Our analysis of the data contained in EudraVigilance confirms the safety signal detected last year by the FDA. Interestingly, for the first time, we show that the association seems the strongest for the intramuscular depot formulation of aripiprazole.