Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study.

BACKGROUND: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations. AIM: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care. METHOD: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland-Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison. RESULTS: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations. CONCLUSION: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

Prescription trends at the end of life in a palliative care unit: observational study.

BACKGROUND: Symptomatic control is essential in palliative care, particularly in end-of-life, in which the pathophysiological changes that characterize this last phase of life strengthen the need to carry out an early therapeutic review. Hence, we aim to evaluate the prescribing pattern at a palliative care unit at two different time points: on admission and the day of the patient's death. METHODS: Quantitative, analytic, longitudinal, retrospective and observational study. Participants were adult patients who were admitted and died in a palliative care unit, in Portugal. Sociodemographic, clinical and pharmacological data were collected, including frequencies and routes of administration of schedule prescribed drugs and rescue drugs, from the day of admission until the day of death. RESULTS: 115 patients were included with an average age of 70.0 ± 12.9 years old, 53.9 were male, mostly referred by the Hospital Palliative Care Support Teams. The most common pathology was cancer, mainly in advanced stage. On admission, the median scheduled prescription was seven and "as needed" was three drugs. On the day of death, a decrease of prescriptions was observed. Opioids were always the most prescribed drugs. Near death, there was a higher tendency to prescribe butylscopolamine, midazolam, diazepam and levomepromazine. The most frequent route of drug administration was oral on admission and subcutaneous on the day of death. CONCLUSIONS: Polypharmacy is a reality in palliative care despite specialist palliative care teams. A reduction of prescribed drugs was verified, essentially due less comorbidity-oriented drugs. Further studies are required to analyse the importance of Hospital Palliative Care Support Teams.

[Medication Reconciliation During Admission to an Internal Medicine Department: A Pilot Study]. / Reconciliação Terapêutica na Admissão de um Serviço de Medicina Interna: Estudo-Piloto.

INTRODUCTION: The purpose of medication reconciliation is to promote patient safety by reducing medication errors and adverse events due to medication discrepancies in transition of care. The aim of this pilot study of medication reconciliation at the time of hospital admission was to identify the necessary resources for its implementation in clinical practice. MATERIAL AND METHODS: Pilot study with 100 patients admitted to an Internal Medicine department between October and December 2019, aged 18 and over, and chronically taking at least one medicine. The best possible medication history was obtained systematically, with subsequent identification, classification and resolution of the discrepancies. RESULTS: The study sample, in general characterized by polypharmacy and by having multiple long-term conditions, presented a mean age of 77.04 ± 13.74 years, being 67.0% male. Overall, 791 discrepancies were identified. Intentional discrepancies were 95.7% and 50.9% of them were documented. The difficulties encountered were mainly related with the access and quality of therapeutic information and communication problems between different healthcare professionals. The key priority resources that were identified were related with the process, tools, and personnel categories. CONCLUSION: The data revealed weaknesses in the clinical records available at the primary/hospital care interface. Optimization of data sources, standardization and informatization of the process, multidisciplinary approach and definition of priority groups were identified as opportunities for optimization.

Introdução: A reconciliação terapêutica visa promover a segurança do doente por meio da redução de erros de medicação e eventos adversos decorrentes de discrepâncias de medicação na transição de cuidados. Foi nosso objetivo realizar um estudo-piloto de reconciliação terapêutica no momento da admissão hospitalar para, a partir dele, identificarmos os recursos necessários para a sua implementação na prática clínica.Material e Métodos: Estudo-piloto com 100 doentes admitidos num serviço de Medicina Interna entre outubro e dezembro de 2019, com mais de 18 anos e a tomar cronicamente pelo menos um medicamento. A melhor história farmacoterapêutica possível foi obtida sistematicamente, com posterior identificação, classificação e resolução das discrepâncias.Resultados: A amostra em estudo, em geral polimedicada e com múltiplas morbilidades, apresentou uma média de idades de 77,04 ± 13,74 anos, sendo 67,0% do sexo masculino. Foram identificadas 791 discrepâncias e as intencionais (95,7%) estavam documentadas em 50,9% das situações. As dificuldades encontradas relacionaram-se principalmente com o acesso e a qualidade da informação terapêutica e com a dificuldade de comunicação entre os diversos profissionais de saúde. Os principais recursos prioritários identificados relacionaram-se com as categorias de processo, ferramentas e pessoal.Conclusão: Os dados revelaram fragilidades nos registos clínicos disponíveis na interface dos cuidados primários/hospitalares. A otimização das fontes de dados, normalização e informatização do processo, atuação multidisciplinar e definição de grupos prioritários foram identificadas como oportunidades de otimização.

Functionalized diterpene parvifloron D-loaded hybrid nanoparticles for targeted delivery in melanoma therapy.

AIM: Parvifloron D is a natural diterpene with a broad and not selective cytotoxicity toward human tumor cells. In order to develop a targeted antimelanoma drug delivery platform for Parvifloron D, hybrid nanoparticles were prepared with biopolymers and functionalized with α-melanocyte stimulating hormone. Results/methodology: Nanoparticles were produced according to a solvent displacement method and the physicochemical properties were assessed. It was shown that Parvifloron D is cytotoxic and can induce, both as free and as encapsulated drug, cell death in melanoma cells (human A375 and mouse B16V5). Parvifloron D-loaded nanoparticles showed a high encapsulation efficiency (87%) and a sustained release profile. In vitro experiments showed the nanoparticles' uptake and cell internalization. CONCLUSION: Hybrid nanoparticles appear to be a promising platform for long-term drug release, presenting the desired structure and a robust performance for targeted anticancer therapy.

Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

ETHNOPHARMACOLOGICAL RELEVANCE: A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. AIM OF THE STUDY: In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. MATERIALS AND METHODS: The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. RESULTS: The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. CONCLUSIONS: Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies.

Flavan hetero-dimers in the Cymbopogon citratus infusion tannin fraction and their contribution to the antioxidant activity.

Cymbopogon citratus (lemongrass) leaf infusion, a commonly used ingredient in Asian, African and Latin American cuisines, is also used in traditional medicine for the treatment of several pathological conditions; however, little is known about their bioactive compounds. Recent studies revealed the crucial role of the phenolic compounds namely flavonoids and tannins on the infusion bioactivity. Flavonoids have already been characterized; however the tannin fraction of lemongrass infusion is still uncharted. The aim of the present work is to characterize this fraction, and to evaluate its contribution to the antioxidant potential of this plant. Chemical characterization was achieved by HPLC-DAD-ESI/tandem MS and the antioxidant activity was evaluated using DPPH, ABTS and FRAP assays. Hetero-dimeric flavan structures have been described for the first time in lemongrass consisting of apigeniflavan or luteoliflavan units linked to a flavanone, either naringenin or eriodictyol, which may occur as aglycone or glycosylated forms. The antioxidant capacity of the fraction containing these compounds was significantly higher than the infusion, indicating its potential as a source of natural antioxidants.

Interação planta-medicamento: a especificidade da terapêutica cardiovascular / Plant-drug interaction: the specificity of cardiovascular therapy

O presente estudo teve como objetivos caracterizar a situação real do consumo de Plantas Medicinais (PM) numa amostra de pacientes com patologia cardiovascular e identificar potenciais interações entre as PM e a terapêutica farmacológica cardiovascular convencional.O estudo foi realizado numa Farmácia Comunitária em Portugal entre abril e junho de 2014. Dos 128 utentes abordados ao balcão que fazem uso da terapêutica cardiovascular, 65 (51%) faziam uso de PM, seja sob a forma de infusão, suplementos ou medicamentos à base de PM. Desses, 43 (66%) foram entrevistados, tendo 22 (34%) sido excluídos por não terem manifestado interesse em participar no estudo. Através da revisão da medicação efetuada para cada doente foram encontradas um total de 123 interações planta-medicamento, com uma média de 2,9 interações/doente, com potencial para diminuir o sucesso da terapêutica cardiovascular. O presente estudo demonstra como o serviço farmacêutico da revisão da medicação pode ser utilizado para otimizar a terapêutica dos doentes cardiovasculares quando estes tomam medicamentos e PM em simultâneo, o que evidencia a função do farmacêutico na sensibilização da população, no sentido de evitar situações prejudiciais para a saúde e bem estar do doente.

Changes in the activities of semicarbazide-sensitive amine oxidase in inferior mesenteric artery segments and in serum of patients with type 2 diabetes.

This study aimed to evaluate the semicarbazide-sensitive amine oxidase (SSAO) activity in human arterial tissues and in serum of patients with type 2 diabetes. The SSAO activity, with (14)C-benzylamine as substrate, was measured in homogenates of human inferior mesenteric arteries obtained at surgery, from 10 patients with type 2 diabetes and 16 non-diabetic patients and in the serum of 39 patients with type 2 diabetes and 40 non-diabetic control patients. The SSAO activity in the homogenates of vascular tissue was significantly lower in the diabetics than in the non-diabetics (P = 0.001). The SSAO activity in the serum of patients with type 2 diabetes was higher when compared with control group (P = 0.0001). In conclusion, the SSAO activity increased in the serum and decreased in the arterial tissue. These findings suggest damage in the vascular tissue and support the hypothesis that serum SSAO may be a useful biochemical marker for diabetes.

Complexos de inclusão de indometacina com hidroxipropil-beta-ciclodextrina: estudos de dissolução e coeficiente de partição / Inclusion compounds of indomethacin with hydroxypropyl-beta-cyclodextrin: dissolution profile and partition coefficient evaluation

A indometacina, antiinflamatório não-esteróide, é praticamente insolúvel em água. A hidroxipropil-beta-ciclodextrina confere aos fármacos nela incluídos melhores características de solubilidade. A formação de complexos com indometacina protege da hidrólise, aumentando a solubilidade. O objetivo desse trabalho foi estudar a influência da complexação por liofilização e por spray-dried, na dissolução e coeficiente de partição. Os resultados dos estudos de dissolução dos complexos de inclusão obtidos por liofilização quando comparados com os obtidos por spray-dryer, apresentam quer maior velocidade de dissolução quer melhor eficiência de dissolução. Os resultados da análise do coeficiente de partição, com ambos os métodos de complexação, confirmam a teoria de que são várias as forças intervenientes neste processo e não é só a fração livre de fármaco que condiciona o transporte para a fase orgânica, reforçando a importância do pH do meio. No estudo com o tampão fosfato pH 7,0, as variações no grau de transporte pela adição de ciclodextrina são muito pequenas, não ocorrendo alteração significativa dos valores de Log P*, verificando-se alterações mais significativas quando se utiliza o tampão fosfato pH 5,5. A complexação aumentou a capacidade de solubilização e dissolução da indometacina, a qual tem caráter lipófilo, sem alterar as características que lhe permitem ter boa capacidade de difusão através de membranas biológicas.

Aspectos biofarmacêuticos da formulação de medicamentos para neonatos. Fundamentos da complexação de indometacina com hidroxipropil-"beta"-ciclodextrina para tratamento oral do fechamento do canal arterial / Biopharmaceutical aspects of drugs formulations for neonatology. Rational for indomethacin's complexation with hydroxypropyl-

A terapêutica farmacológica em recém-nascidos confronta-se, por um lado, com um organismo sujeito a marcadas alterações biológicas, resultantes da composição orgânica e da maturação funcional, que decorre a diferentes graus em crianças com a mesma idade, determinando modificações no perfil farmacocinético e farmacodinâmico e, por outro lado, com a necessidade efetiva da utilização de fármacos. Para dar resposta à necessidade de tratamento destes doentes, recorre-se à utilização de medicamentos off label, sendo esta uma prática com um elevado risco de segurança e de eficácia, na ausência de informação acerca da estabilidade, solubilidade e biodisponibilidade...