Exploring the impact of pharmacogenetics on personalized medicine: A systematic review. / [Artículo traducido] Exploración del impacto de la farmacogenética en la medicina personalizada: una revisión sistemática.

INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualized dosing", "clinical routine" and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by two investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNF-α agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.

Boldness predicts foraging behaviour, habitat use and chick growth in a central place marine predator.

Animal personality can shape individual's fitness. Yet, the mechanistic relationship by which individual's personality traits lead to variations in fitness remains largely underexplored. Here, we used novel object tests to measure boldness of chick-provisioning Cory's shearwaters (Calonectris borealis) from a coastal colony off west Portugal, and deployed GPS loggers to study their at-sea behaviour and distribution. We then tested whether boldness predicts individual differences in adult's trophic ecology and variations in chick growth, to assess potential implications of personality-specific foraging behaviours. Foraging effort was higher for shyer than for bolder individuals, which, during short forays, exhibited larger foraging ranges, and foraged in regions of higher and more variable bathymetry. This suggests that nearby the colony bolder individuals expanded their foraging area to maximize resource acquisition and increase the probability of foraging success. When endeavouring to longer distances, bolder individuals exhibited comparably shorter foraging ranges and targeted low bathymetry regions, likely with enhanced prey availability, while shyer individuals exhibited much larger foraging ranges indicating greater flexibility when foraging in oceanic realms. Despite such differences between bolder and shyer individuals their isotopic niches were similar. Yet, chicks raised by bolder parents grew at a faster rate than those raised by shyer parents. Together, our results suggest that differences in resource acquisition strategies could play a key role through which individual's boldness may influence breeding performance, even when individuals have similar isotopic preferences.

Refractory Hidradenitis Suppurativa: A Diagnosis to Consider.

Hidradenitis suppurativa is a chronic inflammatory disease associated with multiple comorbidities, and its association with lymphoma has recently been a topic of debate. However, it is still controversial whether this risk can be attributed to the disease itself or whether it has any relationship with immunosuppressive treatment. Here, we describe the case of a patient with severe perianal hidradenitis suppurativa treated with methotrexate and infliximab, whose exacerbation with persistence of severe symptoms refractory to adequate treatment led to the diagnosis of diffuse large non-Hodgkin B-cell lymphoma. It was decided to perform a colostomy to improve perianal sepsis, and immunochemotherapy was proposed.

A hidradenite supurativa é uma doença inflamatória crónica associada a múltiplas comorbilidades e a sua associação com doenças linfoproliferativas tem sido, recentemente, um tema de debate. No entanto, é controverso se esse risco pode ser atribuído à própria doença ou se tem relação com o tratamento imunossupressor. Descrevemos o caso de um doente com hidradenite supurativa perianal grave tratada com metotrexato e infliximab, cuja exacerbação com persistência de sintomas graves refratários ao tratamento adequado levou ao diagnóstico de linfoma não-Hodgkin difuso de grandes células B. Optou- se pela realização de colostomia para melhoria da sépsis perianal e início de imunoquimioterapia.

Dynamics and effects of plastic contaminants' assimilation in gulls.

Polybrominated diphenyl ethers are persistent disrupters assimilated by organisms, yet little is known about their link to plastic ingestion and health effects. In an experiment, two groups of yellow-legged/lesser black-backed gulls (Larus michahellis/Larus fuscus) were fed plastics with BDE99 to assess leaching into brain, preen oil, liver and fat tissues and evaluate effects on health and stress parameters. Although most plastic was regurgitated, we observed a clear relation between plastic ingestion and chemical leaching. BDE99 exhibited higher levels in brain tissue of gulls from the plastic groups. Also, only values of cholinesterases measured in plasma were significantly reduced in the 'plastic' groups. Cholinesterase activity in the brain also tended to decrease, suggesting a negative effect in gulls' neurofunction. Results indicate that chemical leaching occurs, even when plastics stay in the stomach for a short period of time and showed that this can affect gulls' health.

Exploring the impact of pharmacogenetics on personalized medicine: A systematic review.

INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.

Omega-3 enriched chick diet reduces the foraging areas of breeders in two closely related shearwaters from contrasting marine environments.

Seabirds have evolved several life-history characteristics to help buffer environmental stochasticity. However, particularly during the breeding season, seabirds may be affected by reductions in prey availability and localised oceanographic conditions caused by variations in the environment. The increase in sea surface temperature, triggered by accelerated global warming, is impairing phytoplankton production of omega-3 fatty acids (FAs). Here, we assessed the ecological role of omega-3 FAs on chick development and subsequently on breeder foraging behaviour in two closely related shearwater species foraging in contrasting marine environments. We supplemented chicks with omega-3 FA pills or with control placebo pills and monitored chick growth, chick health status and breeder at-sea foraging behaviour using global positioning system devices. We found that omega-3 chick supplementation reduced the 95% kernel utilization distribution of short trips of Cape Verde shearwaters, but overall, breeders kept a similar foraging pattern between treatments, potentially influenced by predictable prey patches off the West African coast. In contrast, for Cory's shearwaters, the parents of the omega-3 group greatly reduced the foraging effort. This suggests that the proximity to productive prey patches around the colony may help birds to adjust their effort and, therefore, energy expenditure, to changes in the development of their offspring, as driven by their nutritional status. Overall, our results suggest a link between a chick diet enriched in omega-3 FAs and parental foraging effort, providing insight into their ability to cope with a changing and increasingly stochastic marine environment.

DNA metabarcoding to assess prey overlap between tuna and seabirds in the Eastern tropical Atlantic: Implications for an ecosystem-based management.

Overfishing has been drastically changing food webs in marine ecosystems, and it is pivotal to quantify these changes at the ecosystem level. This is especially important for ecosystems with a high diversity of top predators such as the Eastern Atlantic marine region. In this work we used high-throughput sequencing methods to describe the diet of the two most abundant tuna species, the Skipjack tuna (Katsuwonus pelamis) and the Yellowfin tuna (Thunnus albacares), highly targeted by fisheries off west Africa. We also explored prey diversity overlap between these tuna species and the seabird species breeding in Cabo Verde that are most likely to share prey preferences and suffer from bycatch, the Brown booby (Sula leucogaster) and Cape Verde shearwater (Calonectris edwardsii). Overall, the diet of both tuna species was more diverse than that of seabirds. Skipjack tuna diet was dominated by prey from lower trophic levels, such as krill, anchovies, and siphonophores, while the Yellowfin tuna diet was mainly based on epipelagic fish such as flying and halfbeak fishes. Some of the most abundant prey families detected in the Yellowfin tuna diet were shared with both seabird species, resulting in a high prey diversity overlap between this tuna species and seabirds These results have implications for the management of tuna fisheries in the Eastern Tropical Atlantic, because a large decrease of both tuna species might have cascading effects on both primary and secondary consumer levels, and the decrease of these underwater predators may have implications on the viability of tropical seabird populations.

A century of mercury: Ecosystem-wide changes drive increasing contamination of a tropical seabird species in the South Atlantic Ocean.

Mercury (Hg) is a highly toxic metal that adversely impacts human and wildlife health. The amount of Hg released globally in the environment has increased steadily since the Industrial Revolution, resulting in growing contamination in biota. Seabirds have been extensively studied to monitor Hg contamination in the world's oceans. Multidecadal increases in seabird Hg contamination have been documented in polar, temperate and subtropical regions, whereas in tropical regions they are largely unknown. Since seabirds accumulate Hg mainly from their diet, their trophic ecology is fundamental in understanding their Hg exposure over time. Here, we used the sooty tern (Onychoprion fuscatus), the most abundant tropical seabird, as bioindicator of temporal variations in Hg transfer to marine predators in tropical ecosystems, in response to trophic changes and other potential drivers. Body feathers were sampled from 220 sooty terns, from museum specimens (n = 134) and free-living birds (n = 86) from Ascension Island, in the South Atlantic Ocean, over 145 years (1876-2021). Chemical analyses included (i) total- and methyl-Hg, and (ii) carbon (δ1³C) and nitrogen (δ15N) stable isotopes, as proxies of foraging habitat and trophic position, respectively, to investigate the relationship between trophic ecology and Hg contamination over time. Despite current regulations on its global emissions, mean Hg concentrations were 58.9% higher in the 2020s (2.0 µg g-1, n = 34) than in the 1920s (1.2 µg g-1, n = 107). Feather Hg concentrations were negatively and positively associated with δ1³C and δ15N values, respectively. The sharp decline of 2.9 ‰ in δ1³C values over time indicates ecosystem-wide changes (shifting primary productivity) in the tropical South Atlantic Ocean and can help explain the observed increase in terns' feather Hg concentrations. Overall, this study provides invaluable information on how ecosystem-wide changes can increase Hg contamination of tropical marine predators and reinforces the need for long-term regulations of harmful contaminants at the global scale.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Efficacy of diet on fatigue, quality of life and disability status in multiple sclerosis patients: rapid review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis is an inflammatory and neurodegenerative disease. People with multiple sclerosis (pwMS) experience chronic fatigue which is difficult to deal with therapeutically and greatly affects health-related quality of life (QOL). PwMS are aware of the lack of generalized dietary advice related to their disease, leading to self-experimentation with diet. It is necessary to provide objective information about dietary interventions for pwMS. We aim to provide an objective synthesis of the evidence for efficacy and safety of specific diets in pwMS through a rapid review and meta-analyses of randomized controlled trials (RCTs), examining symptomatic fatigue (MFIS), QOL, Expanded-Disability-Status-Scale (EDSS), and severe adverse events. METHODS: We have carried out a rapid review (MEDLINE and EMBASE) up to December 2021, with PRISMA methodology, and meta-analyses, of (RCTs). All statistical analyses were performed using the comprehensive meta-analysis (CMA) -RStudio 4.1.3. The analysis used weighted mean differences (WMD) and a 95% confidence interval (CI) using a random-effects model to compare the effects of the dietary intervention with the control. RESULTS: Eight studies met the inclusion criteria. Of these eight studies, five analyzed EDSS, three MFIS, and three QOL. A total of 515 patients were analyzed. These meta-analyses cumulative evidence support that dietary intervention is associated with a trend of reduction in fatigue (308 patients studied) -the difference between means (SMD) of the control group and intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-, an increase in QOL (77 patients studied), no significant effect on EDSS (337 patients studied), and no severe adverse events. CONCLUSIONS: It is difficult to reach a high level of evidence in dietary studies. Our findings show that dietary intervention is associated with a trend of reduction in fatigue in MS. Taking into account the potential of dietary interventions and the benefit/risk ratio in their favor, neurologists must be aware of the great importance of making interventions on diet in MS if necessary. There are dietary interventions with some evidence of benefit for patients with MS, which could be chosen based on adherence, patient preferences, and individual outcomes. Large prospective clinical trials are needed to shed further light on this topic.

Design and implementation of an online tool for managing the availability of high-cost perishable medicines.

Introduction: Due to their impact on healthcare systems, the sustainability and optimization of high-cost drugs is an issue of concern for several countries. Different strategies have been implemented such as centralized purchasing to optimize budgetary resources. However, there is still a need for a mechanism to optimize these drugs further. Methods: We conducted this prospective multicenter intervention study in five hospitals in the Andalusian Public Health System of Cádiz (Spain) between July 2019 and September 2021. We developed an online website (Farmastock) and implemented it to determine the availability of high-cost, low-use, and near-expiry medicines in each hospital. We used a simple analysis using operational variables to assess the project intervention's savings impact on managing these high-cost drugs. Results: The implementation of Farmastock in Cádiz resulted in savings of 675,757.52 € for the Andalusian Public Health System, with 238 medicines transferred out of the 373 available. Of these medicines offered, the most considerable percentage were medicines used for pathologies with high clinical instability and accounted for nearly 80% of the medicines optimized by the tool. Conclusions: Farmastock allowed the Andalusian Public Health System to make substantial financial savings by not making new purchases of high-cost drugs available in other centers of this health network that were not being used. Therefore, this tool is a very efficient measure to contribute to the sustainability of the APHS and could be implemented in more hospitals soon.

Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

O tofacitinib surgiu como uma nova terapêutica para a colite ulcerosa. A rapidez da sua absorção, metabolismo e melhoria clínica tornam-no uma opção apelativa como terapêutica de resgate na colite ulcerosa aguda grave (termo em inglês ­ ASUC), entidade esta com opções terapêuticas limitadas em doentes com longo curso de doença e falência prévia a múltiplos fármacos. A abordagem da ASUC neste contexto é desafiante, salientando-se a necessidade de novos fármacos e dados reais sobre a sua eficácia e segurança. Descrevemos dois casos de episódios agudos nos quais o tofacitinib foi utilizado como terapêutica de resgate.

Foraging costs drive within-colony spatial segregation in shearwaters from two contrasting environments in the North Atlantic Ocean.

Foraging spatial segregation is frequent in central-place foragers during the breeding season, but very few studies have investigated foraging spatial segregation between adjacent sub-colonies. Here, we assessed for within-colony differences in the at-sea distribution, habitat use, trophic ecology and chick growth data of two Calonectris colonies differing in size, and breeding in two different environments in the North Atlantic Ocean. For this, we GPS tracked 52 Cory's shearwaters (Calonectris borealis) breeding in 2 small sub-colonies at Berlenga Island (Portugal) and 59 Cape Verde shearwaters (Calonectris edwardsii) breeding in 2 sub-colonies differing greatly in size at Raso Islet (Cabo Verde), over 2 consecutive breeding seasons (2017-2018), during chick-rearing. Cory's shearwaters from the two sub-colonies at Berlenga Island broadly overlapped in repeatedly used foraging patches close to the colony. In contrast, the foraging distribution of Cape Verde shearwaters was partially segregated in the colony surroundings, but overlapped at distant foraging areas off the west coast of Africa. Despite spatial segregation close to the colony, Cape Verde shearwaters from both sub-colonies departed in similar directions, foraged in similar habitats and exhibited mostly short trips within the archipelago of Cabo Verde. These results, corroborated with similar trophic ecology and chick growth rates between sub-colonies, support the idea that foraging spatial segregation in the colony surroundings was not likely driven by interference competition or directional bias. We suggest that high-quality prey patches are able to shape travel costs and foraging distribution of central-place foragers from neighbouring sub-colonies.

Adverse events reported after administration of BNT162b2 and mRNA-1273 COVID-19 vaccines among hospital workers: a cross-sectional survey-based study in a Spanish hospital.

BACKGROUND: The World Health Organization declared COVID-19 a pandemic in March 2020. The first vaccine became available in December, with practically no post-marketing data. METHODS: An analytical cross-sectional survey-based study was conducted in a third-level hospital in Spain between March and April 2021 to describe the difference in adverse events with the BNT162b2 and mRNA-1273 COVID-19 vaccines. The participants were hospital workers who completed a survey voluntarily at least 14 days after the last vaccine. The STROBE checklist was followed. RESULTS: One thousand two hundred and forty-nine respondents completed the survey; 48% (599) received mRNA-1273 and 52% (650) BNT162b2. Fourteen thousand four hundred and two adverse reactions were recorded, 6896 local (3939 with mRNA-1273 and 2957 with BNT162b2 (6.6 vs 4.4 reactions per patient)) and 7506 systemic (4460 with mRNA-1273 and 3046 with BNT162b2 (7.4 vs 4.7 per patient)). Local reactions were more frequent after the first dose, while systemic reactions were higher after the second, for both vaccines and in a higher percentage with mRNA-1273 compared to BNT162b2 (p-value<0.05). CONCLUSIONS: Licensed mRNA vaccines were highly safe when administered under post-marketing conditions among working-age adults. The main adverse events were mild, although they occurred in most patients, especially after the mRNA-1273 vaccine.

Effectiveness and safety of topical 15% resorcinol in the management of mild-to-moderate hidradenitis suppurativa: A cohort study.

Antibiotics remain one of the main treatment alternatives in mild-to-moderate hidradenitis suppurativa. The use of topical 15% resorcinol reduces antibiotic pressure and the generation of resistance. However, knowledge on its efficacy and safety is limited. This single-center, prospective, follow-up cohort study evaluated topical 15% resorcinol every 12-h response at 16 weeks. Those individuals with mild-to-moderate hidradenitis suppurativa (Hurley I-II) who started treatment with topical resorcinol monotherapy between April 2019 and May 2020 were eligible for follow-up. The primary endpoint for effectiveness was the proportion of patients who achieved an overall clinical response (complete or partial response) at week 16, evaluated as intention-to-treat. Responses were measured according to the Hidradenitis Suppurativa Clinical Response index. Target lesion size was measured clinically and by ultrasonography. Quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire. Safety was measured by recording the adverse events reported during the follow-up period. A total of 32 patients were enrolled (mean age, 40.1 years [95% confidence interval, 35.7-44.4]; women, 20 [62.5%]; Hurley I, 17 [53.1%]). Under the intention-to-treat analysis, 68.8% (n = 22) of the patients achieved a clinical response. A ≥50% reduction in the size of the main lesion was observed in 56.3% of the patients (n = 18). Some 65.6% (n = 21) of the patients had a ≥50% reduction (improvement) in their baseline DLQI score. Fifty percent of patients who completed the follow-up period experienced adverse events, all of which were local, mild, and transient and did not lead to discontinuation of resorcinol. To conclude, in this cohort study, topical 15% resorcinol was shown to be effective for mild-to-moderate hidradenitis suppurativa and to have a positive impact on quality of life with an acceptable safety profile.

Compatibility of prolonged infusion antibiotics during Y-site administration.

BACKGROUND: Antimicrobial resistance is a threat to global public health. The use of prolonged infusions in the hospital setting for certain antimicrobials is widely increasing in order to improve their efficacy and safety, including resistance development. Due to limited vascular access, it is important to clarify whether they can be infused through the same line with other drugs during Y-site administration. AIM: The aim of this review is to update and summarize the evidence on Y-site compatibility of antibacterial agents administered as prolonged infusions in intensive care units (ICUs). STUDY DESIGN: A literature review of PubMed, EMBASE and Trissel's Handbook on Injectable Drugs databases was conducted on the compatibility of selected antimicrobials administered simultaneously at a Y-site connection with parenteral nutrition and other widely used drugs in ICUs. All articles published up to October 30, 2021, in English or Spanish were included, regardless of the type of publication (original articles, case reports, letters, etc.). Eligible antimicrobials were those that can be administered as prolonged infusions: ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ceftolozane/tazobactam, ceftaroline, cloxacillin, ceftobiprole, vancomycin and fosfomycin. RESULTS: A total of 1302 drug-to-drug potential combinations were explored, 196 (15.05%) were found to be incompatible, and in 541 (41.55%), data were not available. The results were presented in a simple 2-dimensional consultation chart as a quick reference for health care professionals. CONCLUSIONS: This review provides useful and reliable information on the compatibility of antimicrobials administered as Y-site infusion with other drugs commonly used in the critical setting. This review contributes to patient safety in nursing practice. RELEVANCE TO CLINICAL PRACTICE: To our knowledge, this is the first review on Y-site compatibility of antimicrobials used as prolonged infusions with other commonly used drugs, including anti-emetics, analgesics and anti-epileptic and parenteral nutrition. The results of the current review need to be addressed to promote the knowledge sharing between health professionals and improve the quality and safety of patients. We believe that this review may serve as a simple and effective 2-dimensional updated drug-to-drug compatibility reference chart for critical care nurses.

Formulation, long-term physicochemical and microbiological stability of 15% topical resorcinol for hidradenitis suppurativa.

OBJECTIVES: Topical resorcinol 15% is a self-treatment for painful hidradenitis suppurativa nodules and abscesses with good results in reducing pain and lesion duration. The aim of this study is to establish a 15% topical resorcinol formula, to develop a physicochemical and microbiological stability study and to further determine the compounding shelf-life in different package conditions following the European Pharmacopoeia (Ph. Eur.) specifications. METHODS: Physicochemical and microbiological stability studies of the formulation were conducted for 12 months at room temperature (25°C±2°C) in different package conditions: aluminium tubes (aluminium A7-99.7% varnish DF-6172), plastic tubes (low density polyethylene) and amber plastic containers (polyethylene terephthalate). High performance liquid chromatography (HPLC) was developed as a method of indicating the stability of the resorcinol formulation. A microbiological growth assay was also validated according to the Ph. Eur. Physical properties were inspected to determine parameters such as odour, colour, pH, emulsion phase and extensibility index and its evolution. RESULTS: The HPLC method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. At day 365, visual inspection remained unchanged only for preparations packaged in aluminium tubes. The pH did not vary by more than 0.3 units in all conditions. The extensibility index decreased in the preparations packaged in plastic and amber plastic containers. HPLC analysis conducted over 1 year did not show a degradation greater than 7% of resorcinol in the preparation in plastic and aluminium packages. The ability of ATCC strains to grow in resorcinol formulation was confirmed under the suitability test. Resorcinol packed in aluminium tubes achieved microbiological stability at day 365. CONCLUSIONS: Only the formulation package in aluminium tubes showed physicochemical and microbiological stability of resorcinol for 12 months at room temperature (25°C±2°C).

Accumulation of chemical elements and occurrence of microplastics in small pelagic fish from a neritic environment.

The assessment of contaminant exposure in marine organisms often focuses on the most toxic chemical elements from upper trophic level species. Information on mid-trophic level species and particularly on potentially less harmful elements is lacking. Additionally, microplastics have been considered emergent contaminants in aquatic environments which have not been extensively studied in species from mid-trophic levels in food chains. This study aims to contribute to an overall assessment of environmental impacts of such chemicals in a community of small pelagic fish in the North Atlantic. The concentrations of 16 chemical elements, rarely simultaneously quantified (including minerals, trace elements and heavy metals), and the presence of microplastics were analysed in sardines (Sardina pilchardus) and mackerels (Scomber spp. and Trachurus trachurus) sampled along the Portuguese coast. Biochemical stress assessments and stable isotope analyses were also performed. The chemical element concentrations in S. pilchardus, T. trachurus, and Scomber spp. were relatively low and lower than the levels reported for the same species in the North Atlantic and adjacent areas. No clear relationships were found between chemical elements and oxidative damage in fish. However, the concentration of several chemical elements showed differences among species, being related with the species' habitat use, trophic niches, and specific feeding strategies. The presence of plastic pieces in the stomachs of 29% of the sampled fishes is particularly concerning, as these small pelagic fish from mid-trophic levels compose a significant part of the diet of humans and other top predators. This study highlights the importance of multidisciplinary approaches focusing on the individual, including position data, stable isotopes, and oxidative stress biomarkers as complementary tools in contamination assessment of the marine mid-trophic levels in food chains.