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CONTEXT Doctors caring for patients with life-limiting illness are often exposed to emotional distress. OBJECTIVES We aimed to explore the experiences and perceptions of junior doctors working full-time in a palliative care rotation. We examined the lessons junior doctors learnt in managing their emotions as they face patients' death on a daily basis. METHODS We conducted a qualitative study with seven focus group discussions involving 21 junior doctors (medical officers and residents). Data was analysed using qualitative thematic analysis to identify the themes related to the perceived challenges of these junior doctors and how they managed the struggles. Interviews were conducted with junior doctors who spent at least two months in a palliative care unit in a tertiary hospital or an inpatient hospice. RESULTS Junior doctors caring for dying patients in a palliative care rotation faced internal conflicts. Conflicting feelings arose due to differing expectations from their pre-conceived notions of their roles as doctors. Two main themes of internal struggles were i)Professional distancing and emotional detachment ii)Prognostic uncertainty and when to withhold and withdraw medical treatments. Coping strategies which helped included mentoring and role modelling provided by palliative care physicians, reframing their care experiences and reflection to find meaning in their work. CONCLUSIONS A palliative care rotation exposes junior doctors to emotionally overwhelming experiences. With proper guidance, this exposure is useful in teaching junior doctors important coping strategies, allowing learning to occur at a deeper level. In this paper, we report the development and viscoelastic properties of hyaluronic acid formulations (HA5, HA30, and HA60, containing 0.5, 3, and 6% HA, respectively) loaded with carvacrol prodrugs (WSCPS) with antibacterial properties. learn more Notably, antimicrobial studies revealed that WSCP1-2 in both HA5 and HA30 formulations showed the best minimum inhibitory concentration (MIC) values against Enterococcus faecium (128 mg/L) and Enterococcus faecalis (256 mg/L) compared to those of carvacrol alone or in formulations with HA. Moreover, rheological analyses showed that HA30 composites exhibited a semi-solid consistency, while HA5 formulations possessed a fluid consistency. Considering these data, HA30 is a useful formulation which guarantees a good percentage of prodrug release (e.g., 30 and 60% for WSCP1 and 2, respectively) as well as a texture suitable for topical administration to treat wounds and/or skin infections. Lacidipine is a potent dihydropyridine calcium channel blocker used for management of hypertension and atherosclerosis. The drug has low and fluctuating oral bioavailability owing to its extensive hepatic first-pass metabolism and reduced water solubility. Accordingly, this work aimed at overcoming the aforementioned challenges through the formulation of intranasal nano-sized lacidipine glycerosomes. Box-Behnken was successfully employed for the formulation and in vitro optimization of the glycerosomes. Statistical analysis revealed that cholesterol concentration exhibited a significant effect on the vesicle size, while Phospholipon® 90G and glycerol concentrations exhibited significant effects on both entrapment efficiency and deformability index. The optimized formulation showed spherical shape, good deformability, vesicular size of 220.25 nm, entrapment efficiency of 61.97%, and enhanced ex vivo permeation by 3.65 fold compared to lacidipine suspension. Confocal laser scattering microscope revealed higher penetration depth via nasal mucosa for rhodamine labelled glycerosomes (up to 60 µm) in comparison to rhoadamine dye solution (26 µm). In addition, the optimized lacidipine glycerosomes caused significant reduction in methylprednisolone acetate-induced hypertension in rats for up to 24 hours in comparison to oral drug suspension. Histopathological assessment showed intact nasal mucosal epithelial lining with no signs of inflammation or necrosis confirming the safety and tolerability of the proposed glycerosomes. The declared results highlights the potential of utilizing the proposed glycerosomes as safe and effective platform for intranasal delivery of lacidipine. The purpose of this research was to investigate drug dose, solubility, permeability, and their interplay, as key factors in oral formulation development for lipophilic drugs. A PEG400-based formulation was studied for five doses of the lipophilic drug carbamazepine, accounting for biorelevant dissolution of the dose in the GIT, and in-vivo bioavailability in rats. With the three lower doses (10, 25 and 50 mg/kg), complete in-vitro dissolution was achieved and maintained throughout the experiment with this formulation, while significant precipitation was obtained with higher doses (100 and 200 mg/kg). Likewise, the studied formulation allowed complete bioavailability in-vivo with the three lower doses, while the same formulation allowed only 76% and 42% bioavailability for the 100 and 200 mg/kg doses, respectively. There was good correlation between the in-vitro and in-vivo results. In conclusion, this work demonstrates that the dose is a crucial factor in formulation development; while a given formulation may be optimal for a certain drug dose, it may no longer be optimal for higher doses of the same drug. Hence, the solubility, the permeability, and their interplay, have to be considered in light of the drug dose intended to be administered in order to achieve successful oral formulation development. V.Core-shell nanoparticles (NPs) are attracting increasing interest in nanomedicine as they exhibit unique properties arising from the combined assets of core and shell materials. Porous nanoscale metal-organic frameworks (nanoMOFs) are able to incorporate with high payloads a large variety of drugs. Like other types of NPs, nanoMOFs need to be functionalized with engineered coatings to ensure colloidal stability, control in vivo fate and drug release. To do so, a novel biodegradable cyclodextrin (CD)-based shell was designed in this study. Water soluble γ-CD-citrate oligomers grafted or not with fluorophores were successfully synthesized using citric acid as crosslinker and efficiently anchored onto the surface of porous nanoMOFs. As compared to monomeric CDs, the oligomeric CD coatings could offer higher interaction possibilities with the cores and better possibilities to graft functional moieties such as fluorescent molecules. The amounts of γ-CD-citrate oligomers onto the nanoMOFs were as high as 53 ± 8 wt%.

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