Autogestão da dor crónica no doente em cuidados paliativos: Uma scoping review / Self-management of chronic pain in palliative care patient scoping review

Introdução: Um doente em cuidados paliativos vivencia um conjunto imenso de sintomas que afetam a sua qualidade de vida e que lhe intensificam o sofrimento. O uso de estratégias para a autogestão da dor crónica pode ser encarado como algo eficaz para o controlo da dor potenciando uma melhoria da qualidade de vida. Objetivos: Pretende-se mapear a produção científica acerca da autogestão da dor crónica no doente em cuidados paliativos e conhecer as principais estratégias de controlo da dor crónica em doentes em cuidados paliativos. Metodologia: Foi realizada uma Scoping Review. Para a identificação dos estudos recorreu-se aos motores de busca EBSCO, Web of Science, SCOPUS e literatura cinzenta, entre 01/01/2015 até 31/12/2020. Foram identificados 417 artigos, dos quais selecionamos 9. A seleção e extração dos dados foi realizada de forma independente por dois investigadores, existindo um terceiro em caso de discrepância de opiniões quanto à inclusão/exclusão dos artigos analisados. Resultados: a nível de estratégias farmacológicas a evidência foca-se na administração de fármacos analgésicos nomeadamente na administração de opióides, identificando-os como eficazes. No que diz respeito a estratégias não farmacológicas de autogestão da dor crónica, foram relatadas diversas estratégias, tais como a musicoterapia, a acupuntura, hipnose/auto-hipnose, Reiki, a caminhada, termoterapia (o uso do calor), a crioterapia, o uso do posicionamento, exercícios de fortalecimento muscular, a massagem, o uso da meditação, o uso da neuroestimulação elétrica transcutânea, o uso da espiritualidade e a fisioterapia. Estas intervenções/ estratégias após a análise da sua utilização, demonstraram eficazes. Conclusões: Os estudos analisados nesta Scoping Review, permitem concluir que existem diversas estratégias quer farmacológicas quer não farmacológicas eficazes na autogestão da dor crónica no doente em cuidados paliativos. Apesar destes resultados, são necessários mais investimentos na área e pesquisa mais aprofundada a nível de eficácia das intervenções neste âmbito.

Introduction: A patient in palliative care experiences an immense set of symptoms that affect their quality of life and intensify their suffering. The use of strategies for chronic pain self-management can be seen as something effective for pain control, enhancing an improvement in quality of life. Objectives: It is intended to map the scientific production on the self-management of chronic pain in patients in palliative care and to know the main strategies for controlling chronic pain in patients in palliative care. Methodology: A Scoping Review was conducted. To identify the studies, the search engines EBSCO, Web of Science, SCOPUS and grey literature, between 01/01/2015 to 31/12/2020. A total of 417 articles were identified, of which we selected 9. Data selection and extraction was performed independently by two Results: at the level of pharmacological strategies the evidence focuses on the administration of analgesic drugs, particularly in the administration of opioids, identifying them as effective. With regard to non-pharmacological strategies for chronic pain self-management, a number of strategies have been reported, such as music therapy, acupuncture, hypnosis/self-hypnosis, Reiki, walking, thermotherapy (the use of heat), cryotherapy, the use of positioning, muscle strengthening exercises, massage, the use of meditation, the use of transcutaneous electrical neurostimulation, the use of spirituality and physiotherapy. These interventions/strategies after the analysis of their use have been shown to be effective. Conclusions: The studies analyzed in this Scoping Review allow us to conclude that there are several strategies, both pharmacological and non-pharmacological effective in self-management of chronic pain in patients in care. Despite these results, more investments are needed in the area and further research in terms of effectiveness of interventions in this field.

Multidrug-resistant Klebsiella pneumoniae harboring extended spectrum ß-lactamase encoding genes isolated from human septicemias.

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. We aim to characterize the type of ß-lactamases and the associated resistance mechanisms in ESBL-producing K. pneumoniae isolates obtained from blood cultures in a Portuguese hospital, as well as to determine the circulating clones. Twenty-two cefotaxime/ceftazidime-resistant (CTX/CAZR) K. pneumoniae isolates were included in the study. Identification was performed by MALDI-TOF MS and the antimicrobial susceptibility testing by disk-diffusion. The screening test for ESBL-production was performed and ESBL-producer isolates were further characterized. The presence of different beta-lactamase genes (blaCTX-M, blaSHV, blaTEM, blaKPC, blaNDM, blaVIM, blaOXA-48, blaCMY-2, blaDHA-1, blaFOX, blaMOX, and blaACC) was analyzed by PCR/sequencing in ESBL-producer isolates, as well as the presence of other resistance genes (aac(6')-Ib-cr, tetA/B, dfrA, qnrA/B/S, sul1/2/3) or integron-related genes (int1/2/3). Multilocus-sequence-typing (MLST) was performed for selected isolates. ESBL activity was detected in 12 of the 22 CTX/CAZR K. pneumoniae isolates and 11 of them carried the blaCTX-M-15 gene (together with blaTEM), and the remaining isolate carried the blaSHV-106 gene. All the blaCTX-M-15 harboring isolates also contained a blaSHV gene (blaSHV-1, blaSHV-11 or blaSHV-27 variants). Both blaSHV-27 and blaSHV-106 genes correspond to ESBL-variants. Two of the CTX-M-15 producing isolates carried a carbapenemase gene (blaKPC2/3 and blaOXA-48) and showed imipenem resistance. The majority of the ESBL-producing isolates carried the int1 gene, as well as sulphonamide-resistance genes (sul2 and/or sul3); the tetA gene was detected in all eight tetracycline-resistant isolates. Three different genetic lineages were found in selected isolates: ST348 (one CTX-M-15/TEM/SHV-27/KPC-2/3-producer isolate), ST11 (two CTX-M-15/TEM/SHV-1- and CTX-M-15-TEM-SHV-11-OXA-48-producer isolates) and ST15 (one SHV-106/TEM-producer isolate). ESBL enzymes of CTX-M-15 or SHV-type are detected among blood K. pneumoniae isolates, in some cases in association with carbapenemases of KPC or OXA-48 type.

Chemical Composition, Antioxidant and α-Glucosidase-Inhibiting Activities of the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves.

Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was investigated. A comprehensive analysis of the antioxidant activity of two bilberry leaf extracts was performed. The aqueous extract showed excellent total antioxidant and chelating activity. Its antioxidant activity in the ß-carotene-linoleic acid assay was very good, reaching the activity of the antioxidant standard BHA (93.4 ± 2.3% vs. 95.1 ± 2.4%, respectively). The hydroethanolic extract (ethanol/H2O, 8:2, v/v), on the other hand, was a better radical scavenger and Fe2+ reducing agent. Furthermore, the aqueous extract was able to efficiently increase glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress and restore it to the levels observed in non-hyperglycaemic cells. The hydroethanolic extract strongly inhibited α-glucosidase, with the IC50 statistically equal to the antidiabetic drug acarbose (0.29 ± 0.02 mg/mL vs. 0.50 ± 0.01 mg/mL, respectively). Phytochemical analysis revealed the presence of quercetin and kaemferol derivatives, as well as chlorogenic and p-coumaric acid. The study results indicate that V. myrtillus leaf may have promising properties as a supporting therapy for diabetes.

Subgingival Irrigation with a Solution of 20% Propolis Extract as an Adjunct to Non-Surgical Periodontal Treatment: A Preliminary Study.

Natural products, including propolis, are now frequently used to treat periodontal disease, but there are a few clinical studies in this area. The aim of this randomized clinical trial was to evaluate the effect of subgingival irrigation of periodontal pockets with a hydroalcoholic solution of propolis extract 20% (w/v) as an adjunct to periodontal therapy. Sixteen individuals were divided into a test group (TG), comprised 65 teeth (scaling and root planing + irrigation with propolis solution), and a control group (CG), comprised 62 teeth (scaling and root planing + irrigation with saline solution). Clinical data such as probing depth, plaque index, gingival index and oral hygiene index were collected at baseline (T0) and after 45 (T1), 75 (T2) and 90 (T3) days. Both groups showed significant differences among the evaluated periods. The TG presented more reduction (p < 0.05) of probing depth than CG at T1 and T3. Within the limits of this short-term study, these data suggest that irrigation with a hydroalcoholic solution of propolis extract 20% (w/v) as an adjunct in periodontal treatment was more effective than the mechanical treatment with saline solution in terms of reducing probing depth for up to 90 days from the beginning of treatment.

Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs.

CONTEXT: Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal. OBJECTIVE: To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc. MATERIAL AND METHODS: Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48 h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24 h) was tested using HEP G2 cells and fibroblasts. RESULTS: Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90 mg AAE/g dw and 783.48 mg TE/g dw, respectively). CM had the highest zinc concentration (37.21 mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91 mg/100 g dw). LS was rich in rosmarinic acid (301.71 mg/100 g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830 µg/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content. CONCLUSION: The most promising plants for further studies are CM, LS and GP.

Identification of Predominant Phytochemical Compounds and Cytotoxic Activity of Wild Olive Leaves (Olea europaea L. ssp. sylvestris) Harvested in South Portugal.

This study has been aimed at providing a qualitative and quantitative evaluation of selected phytochemicals such as phenolic acids, flavonoids, oleuropein, fatty acids profile, and volatile oil compounds, present in wild olive leaves harvested in Portugal, as well as at determining their antioxidant and cytotoxic potential against human melanoma HTB-140 and WM793, prostate cancer DU-145 and PC-3, hepatocellular carcinoma Hep G2 cell lines, as well as normal human skin fibroblasts BJ and prostate epithelial cells PNT2. Gallic, protocatechuic, p-hydroxybenzoic, vanillic acids, apigenin 7-O-glucoside, luteolin 7-O-glucoside, and rutin were identified in olive leaves. The amount of oleuropein was equal to 22.64 g/kg dry weight. (E)-Anethole (32.35%), fenchone (11.89%), and (Z)-3-nonen-1-ol (8%) were found to be the main constituents of the oil volatile fraction, whereas palmitic, oleic, and alpha-linolenic acid were determined to be dominating fatty acids. Olive leaves methanol extract was observed to exerted a significant, selective cytotoxic effect on DU-145 and PC-3 cell lines. Except the essential oil composition, evaluated wild olive leaves, with regard to their quantitative and qualitative composition, do not substantially differ from the leaves of other cultivars grown for industrial purposes and they reveal considerable antioxidant and cytotoxic properties. Thus, the wild species may prove to be suitable for use in traditional medicine as cancer chemoprevention.

Prenatal alcohol exposure reduces mandibular calcium and phosphorus concentrations in newborn rats.

Previous studies suggest that prenatal alcohol exposure affects fetal bone development, including bone quality. This study evaluated the chemical composition of mandibles from newborn rats after maternal 20% alcohol consumption before and throughout gestation. Nine rats were initially distributed into three groups: an Alcohol group, Pair-fed group, and Control group. The groups were fed prespecified diets for 8 weeks before and the 3 weeks during pregnancy. At age 5 days, eight newborns from each group were euthanized (total, n = 24). Using energy dispersive spectrometry, we evaluated samples of mandibles from newborns to identify changes in bone mineralization, specifically Ca and P concentrations. Ca and P concentrations were lower in the Alcohol group than in the Control and Pair-fed groups (P = 0.003 and P = 0.001, respectively). In summary, alcohol exposure before and throughout gestation reduces mandibular Ca and P concentrations in newborn rats. (J Oral Sci 58, 439-444, 2016).

Effect of Betula pendula Leaf Extract on α-Glucosidase and Glutathione Level in Glucose-Induced Oxidative Stress.

B. pendula leaf is a common ingredient in traditional herbal combinations for treatment of diabetes in southeastern Europe. Present study investigated B. pendula ethanolic and aqueous extract as inhibitors of carbohydrate hydrolyzing enzymes, as well as their ability to restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress. Phytochemical analysis revealed presence of rutin and other quercetin derivatives, as well as chlorogenic acid. In general, ethanolic extract was richer in phenolic substances than the aqueous extract. Furthermore, a comprehensive analysis of antioxidant activity of two extracts (determined by DPPH and ABTS radical scavenging activity, total antioxidant activity, and chelating activity as well as ferric-reducing antioxidant power) has shown that ethanolic extract was better radical scavenger and metal ion reductant. In addition, ethanolic extract effectively increased cellular glutathione levels caused by hyperglycemia and inhibited α-glucosidase with the activity comparable to that of acarbose. Therefore, in vitro research using B. pendula plant extracts has confirmed their antidiabetic properties.

Recent developments in therapeutic applications of Cyanobacteria.

The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health with numerous biological activities and as a dietary supplement. It is used as a food supplement because of its richness in nutrients and digestibility. Many cyanobacteria (Microcystis sp, Anabaena sp, Nostoc sp, Oscillatoria sp., etc.) produce a great variety of secondary metabolites with potent biological activities. Cyanobacteria produce biologically active and chemically diverse compounds belonging to cyclic peptides, lipopeptides, fatty acid amides, alkaloids and saccharides. More than 50% of the marine cyanobacteria are potentially exploitable for extracting bioactive substances which are effective in killing cancer cells by inducing apoptotic death. Their role as anti-viral, anti-tumor, antimicrobial, anti-HIV and a food additive have also been well established. However, such products are at different stages of clinical trials and only a few compounds have reached to the market.

Development of a beverage benchtop prototype based on sweet potato peels: optimization of antioxidant activity by a mixture design.

A beverage benchtop prototype related to oxidative stress protection was developed based on sweet potato peels phenolics. Formula components were sweet potato peel (Ipomoeas batatas L.) aqueous extract (SPPE), sweet potato leaves water extract (SPLE) and honey solution (HonS). According to linear squares regression (LSR) models, SPLE presented higher additive effect on total phenolic content (TPC), FRAP and DPPH than the other components. All antagonist interactions were not significant. The optimum formula obtained by artificial neural networks (ANN) analysis was 50.0% of SPPE, 21.5% of SPLE and 28.5% of HonS. Predicted responses of TPC, FRAP, DPPH and soluble solids were 309 mg GAE/L, 476 mg TE/L, 1098 mg TE/L and 12.3 °Brix, respectively. Optimization with LSR models was similar to ANN. Beverage prototype results positioned next to commercial vegetable and fruit beverages, thus it has an interesting potential to the market of health and wellness.

In vitro antioxidant activity, phenolic compounds and protective effect against DNA damage provided by leaves, stems and flowers of Portulaca oleracea (Purslane).

This study analyzed the antioxidant properties of Portulaca oleracea L., known as purslane. The samples (leaves, flowers and stems) were collected at two different locations in Portugal: Tavira (L1) and Vendas Novas (L2). Assays for total antioxidant activity, total phenolic content and ferric-reducing antioxidant power were conducted and, for both locations, significantly higher values (P < 0.05) were observed for stems (508.8 and 982.3 mg AAE/100 g DW, 1008.6 and 2285.5 mg GAE/100 g DW, 121.0 and 166.3 mg TE/100 g DW, respectively for each location), than in leaves or flowers. In the DPPH assay, the three-plant parts from L2 reached the 50% inhibition rate in lower concentrations than plants from L1. On the other hand, higher concentrations of total monomeric anthocyanins were found in samples from L1 (95.5, 88.8 and 86.0 mg/L) than in samples from L2 (81.7, 70.5 and 59.8 mg/L). The same was true for phenolic acids, estimated by liquid-chromatography, where methanol extracts were used. Phenolic extracts from all three-plant parts from both locations showed protective effects on DNA against hydroxyl radicals. This work suggests the possibility of benefit to human health from its consumption, related to the high antioxidant activity of purslane, even the stems, usually discarded in daily consumption.

Cytotoxicity and antiangiogenic activity of grandisin.

OBJECTIVES: The antitumoural properties of grandisin, a tetrahydrofuran neolignan from Piper solmsianum, were investigated by in-vitro and in-vivo assays using the Ehrlich ascites tumoural (EAT) model. METHODS: Viability of the tumour cells was evaluated by Trypan blue exclusion and MTT methods, after incubation with grandisin (0.017-2.3 microm). The effects of grandisin on the activity of caspase-3, -6, -8, and -9 were also investigated using colorimetric protease kits. In-vivo studies were performed in EAT-bearing mice treated intraperitoneally with 2.5, 5 or 10 mg/kg grandisin for 10 days. KEY FINDINGS: Grandisin inhibited the growth of EAT cells, by both methods, with IC50 values less than 0.25 microm. The results showed that the activity of all the caspases studied increased in grandisin-treated cells, when compared with control, non-treated cells. Administering grandisin to EAT-bearing mice increased survival of the animals, in a dose-dependent manner. Simultaneously, we detected a 66.35% reduction of intraperitoneal tumour cell burden in the animals treated with 10 mg/kg grandisin. Additionally, in these animals, the marked increase of vascular endothelial growth factor (VEGF) levels, induced by EAT development, was decreased with treatment with grandisin, resulting in a reduction of 32.1% of VEGF levels in the peritoneal washing supernatant, when compared with the control. CONCLUSIONS: The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.