The role of pharmacist in community palliative care-a scoping review.

OBJECTIVES: Dynamic and adaptive services that provide timely access to care are pivotal to ensuring patients with palliative needs experience high-quality care. Patients who have palliative care needs may require symptomatic relief with medicines and, therefore, may engage with community pharmacists frequently. However, there is limited evidence for pharmacists' involvement in community palliative care models. Therefore, a scoping review was conducted to identify pharmacists' role in community palliative care. METHODS: A systematic search strategy was implemented across PubMed, PsychINFO, CINAHL, and Embase databases. Articles were screened by abstract and full text against inclusion and exclusion criteria. KEY FINDINGS: Five articles (two from Australia, two from England, and one from Scotland) met the inclusion criteria and described interventions involving pharmacists in community palliative care. This review has identified that the inclusion of trained pharmacists in community palliative care teams can improve the quality of care provided for patients with palliative needs. Pharmacists are able to undertake medication reviews and provide education to patients and other healthcare professionals on the quality use of palliative care medicines. Additionally, the underutilization of community pharmacists in palliative care, the need for further training of pharmacists, and improved community pharmacy access to patient information to deliver community palliative care were identified. CONCLUSION: Pharmacists can play a vital role in community palliative care to enhance the quality of life of patients. There is a need for greater pharmacist education/training, improved interprofessional communication, improved access to patient information and sustainable funding to strengthen community-based palliative care.

Alleviation of Diabetic Retinopathy by Glucose-Triggered Delivery of Vitamin D via Dextran-Gated Functionalized Mesoporous Silica Nanoparticles.

Diabetic retinopathy (DR) is the most common retinal disorder, developed in 35% of patients with diabetes mellitus. Lower serum levels of 25-hydroxyvitamin D are associated with the increased risk of developing DR. High doses of the active form of vitamin D (VD), on the contrary, for a long period of time may lead to hypercalcemia and an imbalance in the regulation of bone metabolism. Herein, we studied the efficacy of dextran-gated carboxyphenylboronic acid (CPBA)-functionalized mesoporous silica nanoparticles (MSNs) for glucose-sensitive delivery of 1,25-dihydroxyvitamin D3 to modulate cellular oxidative stress and inflammation for managing DR. The physical adsorption technique was employed to load VD onto nanoparticles (263.63 µg/mg (w/w)). In the presence of glucose, the dextran molecules detach from pores, allowing VD to release since glucose has 1,2-cis diol groups which have very high affinity to CPBA. Approximately 75% of VD was released upon exposure to 25 mM glucose at a time point of 10 h, demonstrating glucose-responsive delivery. Furthermore, MSN-CPBA was able to deliver VD in a glucose-dependent manner and improve the bioavailability of VD. In high-glucose-supplemented human retinal cells, MSN-CPBA increased the bioavailability of VD and reduced cellular oxidative stress and inflammation. The results suggested that the VD-loaded nanocarrier exerted remarkable therapeutic capacity in reducing the risk of developing DR. By using MSN-CPBA as a delivery platform with dextran gating, the research proposes an effective treatment approach for improving the bioavailability and effectiveness of a hydrophobic molecule in the treatment of DR.

Educational Interventions in Immigrants for Asthma and COPD: A Systematic Review.

Objective: Asthma and COPD are prevalent respiratory conditions among immigrants, yet many individuals in this population do not effectively utilize available therapies, resulting in exacerbations and limitations in their daily lives. This systematic review seeks to describe asthma/COPD educational interventions specifically tailored for immigrant patients and assess their variability and outcomes, with the ultimate goal of improving self-management and achieving better asthma or COPD control in this population. Design: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A comprehensive literature search was conducted using four electronic databases (CINAHL, PubMed, Embase and PsycInfo). Articles were included if they focused on asthma or COPD interventions conducted in immigrant populations. The Mixed Methods Appraisal Tool was used to assess the quality of included articles. Results: Out of the initial 1173 articles identified, 812 were assessed for eligibility. Six articles met the inclusion criteria for educational interventions targeting immigrants with asthma or COPD. These studies explored the effectiveness of interventions on various immigrant populations using different methodologies including group discussion of photographs and classroom-based interventions. The interventions varied in terms of settings, educational materials, and delivery methods. Positive outcomes were observed in areas such as knowledge, understanding of instructions, and inhaler technique. However, the included studies had limitations in assessing the impact on asthma and COPD self-management and sustainability. Conclusion: More research is needed on asthma and COPD management in immigrants. The interventions included in this review had positive effects on outcomes like inhaler technique and asthma knowledge. However, due to variability in outcome measures, it is difficult to directly compare the interventions. Future studies should include diverse immigrant populations, consider the specific migration status of the immigrants, long-term sustainability of the intervention and use culturally tailored approaches to improve respiratory health in this population.

Momordica cochinchinensis (Gac) Seed Extracts Induce Apoptosis and Necrosis in Melanoma Cells.

Momordica cochinchinensis is a herbal medicine used throughout Asia and this study investigated the antimelanoma potentials and molecular mechanisms of M. cochinchinensis seed with emphasis on extraction to optimise bioactivity. Overall, the aqueous extract was superior, with a wider diversity and higher concentration of proteins and peptides that was more cytotoxic to the melanoma cells than other extraction solvents. The IC50 of the aqueous extract on melanoma cells were similar to treatment with current anticancer drugs, vemurafenib and cisplatin. This cytotoxicity was cancer-specific with lower cytotoxic effects on HaCaT epidermal keratinocytes. Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma.

Coping mechanisms used by pharmacists to deal with stress, what is helpful and what is harmful?

Background: Australian pharmacists encountered increased stressors during the COVID-19 pandemic. This has raised questions regarding the effectiveness of the coping mechanisms used to manage this high work-related stress. Identifying useful and harmful coping mechanisms is critical for providing advice regarding addressing pharmacists' future work-related stress. Objectives: This study aimed to explore the impact of pharmacy work on stress experienced by Australian pharmacists and the coping mechanisms used during the COVID-19 pandemic. This study also aimed to evaluate the pharmacists' perceptions of the impact of these coping mechanisms on their stress. Methods: A cross-sectional study was conducted. Practising pharmacists and interns were recruited to complete an online survey that included the Perceived Stress Scale (PSS), which was used to measure pharmacists' work-related stress, and the Brief-COPE scale, used to assess the coping mechanisms used during the COVID-19 pandemic. The key outcome measure was the PSS score. A multiple regression analysis was used to evaluate the relationship between coping mechanisms and stress levels in a sample of Australian pharmacists. Results: A total of 173 pharmacists and interns were recruited. The mean PSS was 18.02 (SD = 6.7). Avoidant coping mechanisms such as social withdrawal (ß = 0.31; p = 0.0001) were significantly positively associated with work-related stress. In contrast, exercise was significantly negatively associated with work-related stress (ß = -0.21; p = 0.009). The most frequently reported perceived barrier to seeking help was feeling burnt out and underappreciated. Conclusions: This study highlights the association of coping mechanisms used by pharmacists during the COVID-19 pandemic with work-related stress. The study results demonstrate the importance of physical activity and spending time with pets in reducing work-related stress levels. Avoiding harmful coping mechanisms such as social withdrawal and drinking alcohol is recommended. This study also highlights the need for interventional studies to reduce work-related stress levels among pharmacists by addressing useful coping mechanisms.

Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants.

Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS.

Natural antioxidants in the management of Parkinson's disease: Review of evidence from cell line and animal models.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.

Acupuncture versus placebo acupuncture for in vitro fertilisation: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of acupuncture compared to placebo acupuncture for women undergoing in vitro fertilisation (IVF) in a systematic review and meta-analysis. METHODS: A search was conducted in seven English-language biomedical databases from their inception to 3 April 2019 to identify studies evaluating acupuncture as an adjunct to IVF treatment. Randomised controlled trials (RCTs) that compared acupuncture with placebo acupuncture using a non-invasive placebo acupuncture device in women undergoing a fresh or frozen IVF cycle were eligible, as were studies that tested placebo acupuncture as the intervention. Outcomes were clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, live birth rate and adverse events. RESULTS: Eight RCTs involving 3607 women were included. Studies were judged to be low risk for most of the risk of bias domains. Acupuncture around the time of embryo transfer was not significantly different to placebo acupuncture in terms of the clinical pregnancy rate (6 RCTs, 2473 women, risk ratio (RR) = 0.99 (95% confidence interval (CI) = 0.88, 1.11), I2 = 51%, moderate certainty evidence), ongoing pregnancy rate (4 RCTs, 1459 women, RR = 0.88 (95% CI = 0.75, 1.02), I2 = 50%, moderate certainty evidence), miscarriage rate (4 RCTs, 502 women, RR = 1.23 (95% CI = 0.89, 1.71), I2 = 30%, high certainty evidence) or live birth rate (4 RCTs, 1835 women, RR = 0.87 (95% CI = 0.75, 1.01), I2 = 0%, high certainty evidence). Outcomes with placebo acupuncture were not significantly different to usual care. Adverse events relating to acupuncture, such as discomfort and bruising, were mild to moderate. CONCLUSION: Acupuncture administered around the time of embryo transfer did not have a statistically significant effect on IVF outcomes compared with placebo acupuncture.

Recent advances in the management of diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in people with diabetes. The current treatments do not target early stages of disease or impede disease progression. Therefore, the identification of new therapeutic targets, the development of novel therapies targeting early stages of the disease and accurate models that simulate pathological characteristics of this disorder are crucial. This review provides an overview of the pathological mechanisms underlying the development of DR, highlighting the recent advances in current and emerging treatments for DR.

Critical appraisal of commercially available suspending vehicles for extemporaneous compounding of cardiovascular medicines: physical and chemical stability mini review.

Oral liquid formulations are compounded by pharmacists to meet the needs of patients when a suitable commercially available product is not available. To minimize the errors associated with measuring multiple excipients and to enhance the shelf-life of the medicines, commercially available suspending bases are commonly used. This review aims to compare the stability and shelf life of commercially available extemporaneous formulation to traditional formulation methods. Five (5) databases were searched (Pubmed, SCOPUS, Science direct, Embase, and EBSCOhost). Twelve articles, comprising of seven cardiovascular medications (amiodarone, captopril, carvedilol, furosemide, nifedipine, sotalol, and valsartan), met the study inclusion criteria and were reviewed. Chemical stability of the drugs was comparable between the two formulation methods except for furosemide, captopril, and valsartan. The traditional compounding method provided superior stability for furosemide (90 vs. 14 days) and captopril (50 vs. 14 days), while the commercial vehicles provided superior stability for valsartan (90 vs. 14 days). Physical stability tests indicated that sedimentation does occur with both formulation methods. Microbial studies within the data were lacking and further research can be undertaken in this area. This review highlights the importance of assessing the suitability of compounding ingredients prior to preparation of the formulation.

Drug delivery to the lens for the management of cataracts.

Cataracts are one of the most prevalent diseases of the lens, affecting its transparency and are the leading cause of reversible blindness in the world. The clarity of the lens is essential for its normal physiological function of refracting light onto the retina. Currently there is no pharmaceutical treatment for prevention or cure of cataracts and surgery to replace the affected lens remains the gold standard in the management of cataracts. Pharmacological treatment for prevention of cataracts is hindered by many physiological barriers that must be overcome by a therapeutic agent to reach the avascular lens. Various therapeutic agents and formulation strategies are currently being investigated to prevent cataract formation as access to surgery is limited. This review provides a summary of recent research in the field of drug delivery to the lens for the management of cataracts including models used to study cataract treatments and discusses the future perspectives in the field.

L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration.

BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression. OBJECTIVE: To examine L-Sulforaphane as a potential treatment to ameliorate aberrant levels of gene expression and metabolites observed in age-related macular degeneration. METHOD: The in vitro oxidative stress model of AMD was based on the exposure of Adult Retinal Pigment Epithelium-19 cell line to 200µM hydrogen peroxide. The effects of L-Sulforaphane on cell proliferation were determined by MTS assay. The role of GSTM1, VEGFA, DNMT1 and HDAC6 genes in modulating these effects was investigated using quantitative real-time polymerase chain reaction. The metabolic profiling of L-Sulforaphane-treated cells via gas-chromatography massspectrometry was established. Significant differences between control and treatment groups were validated using one-way ANOVA, student t-test and post-hoc Bonferroni statistical tests (p<0.05). RESULTS: L-Sulforaphane induced a dose-dependent increase in cell proliferation in the presence of hydrogen peroxide by upregulating Glutathione-S-Transferase µ1 gene expression. Metabolic profiling revealed that L-Sulforaphane increased levels of 2-monopalmitoglycerol, 9, 12, 15,-(Z-Z-Z)- Octadecatrienoic acid, 2-[Bis(trimethylsilyl)amino]ethyl bis(trimethylsilyl)-phosphate and nonanoic acid but decreased ß-alanine levels in the absence or presence of hydrogen peroxide, respectively. CONCLUSION: This study supports the use of L-Sulforaphane to promote regeneration of retinal cells under oxidative stress conditions.

Release kinetics of somatostatin from self-assembled nanostructured hydrogels.

Somatostatin-14 is a native neuropeptide with widespread functions in the body. Self-assembly of somatostatin-14 into amyloid-like nanofibrils has been previously demonstrated in aqueous media. We here hypothesize that the somatostatin nanofibrils can form a stable depot that release monomers in a controlled manner. This study aims to investigate if somatostatin monomers are released from physical hydrogels formed in water and in the presence of electrolytes. The release kinetics of the somatostatin monomers is investigated for the first time. This is correlated with the rheological properties of the hydrogels formed. We demonstrate that at the concentrations tested, there is release of somatostatin monomers from the hydrogels following a novel hybrid model of zero-order and first-order release. In the presence of electrolytes, somatostatin hydrogels demonstrated higher elastic moduli (G') which correlates to the narrower and higher density of nanofibrils observed with TEM. The presence of electrolytes resulted in a slower release of the somatostatin monomers and in a lower cumulative percentage released over 48 hrs. It is questionable that the concentrations released will be therapeutically effective. However, self-assembled somatostatin hydrogels have the potential to act as a depot for ocular drug delivery.

Mimicking the ocular environment for the study of inflammatory posterior eye disorders.

The common inflammatory posterior eye disorders, age-related degeneration and glaucoma often lead to irreversible vision loss. Current treatments do not target early stages or prevent disease progression. Consequently, the identification of biomarkers or early disease models that can accurately mimic the pathological processes involved is essential. Although none of the existing models can recapitulate all pathological aspects of these disorders, these models have revealed new therapeutic targets. Efforts to accurately phenotype eye disorders at various disease stages are warranted to generate a 'super' model that can replicate the microenvironment of the eye and associated pathological hallmarks effectively.

Therapeutic uses of somatostatin and its analogues: Current view and potential applications.

Somatostatin is an endogeneous cyclic tetradecapeptide hormone that exerts multiple biological activities via five ubiquitously distributed receptor subtypes. Classified as a broad inhibitory neuropeptide, somatostatin has anti-secretory, anti-proliferative and anti-angiogenic effects. The clinical use of native somatostatin is limited by a very short half-life (1 to 3min) and the broad spectrum of biological responses. Thus stable, receptor-selective agonists have been developed. The majority of these somatostatin therapeutic agonists bind strongly to two of the five receptor subtypes, although recently an agonist of wider affinity has been introduced. Somatostatin agonists are established in the treatment of acromegaly with recently approved indications in the therapy of neuroendocrine tumours. Potential therapeutic uses for somatostatin analogues include diabetic complications like retinopathy, nephropathy and obesity, due to inhibition of IGF-1, VEGF together with insulin secretion and effects upon the renin-angiotensin-aldosterone system. Wider uses in anti-neoplastic therapy may also be considered and recent studies have further revealed anti-inflammatory and anti-nociceptive effects. This review provides a comprehensive, current view of the biological functions of somatostatin and potential therapeutic uses, informed by the wide range of pharmacological advances reported since the last published review in 2004 by P. Dasgupta. The pharmacology of somatostatin receptors is explained, the current uses of somatostatin agonists are discussed, and the potential future of therapeutic applications is explored.

IGF-1 signaling via the PI3K/Akt pathway confers neuroprotection in human retinal pigment epithelial cells exposed to sodium nitroprusside insult.

The pathological increase in the levels of the second messenger nitric oxide (NO) in the vitreous cavity and retina leads to injury and cell death of the retinal pigment epithelium (RPE) cells and eventually may contribute to the occurrence and development of diabetic retinopathy. In this study, we developed a cellular model of retinopathy using D407 cells (a human RPE cell line) exposed to sodium nitroprusside (SNP) and investigated the protective effect of the insulin-like growth factor-1 (IGF-1) towards this insult. Cell death and apoptosis were examined by the methyl thiazolyl tetrazolium assay and Hoechst staining, respectively. Specific inhibitors were used and phosphorylation of relevant signaling proteins was determined by Western blotting. SNP, in a concentration-dependent fashion, increased the production of reactive oxygen species (ROS) and lipid peroxidation process causing cell death by apoptosis of D407 cells. IGF-1, in a time- and dose-dependent manner, conferred protection towards SNP-mediated insult. Both phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) were activated by IGF-1 in relation to the protective effect. Blockade of the PI3K/Akt pathway abolished the protective effect of IGF-1 whereas inhibition of the MAPK pathway was ineffective. SNP decreased the phosphorylation of Akt in the cells while IGF-1 reversed this inhibitory effect. These results indicate that the protective effect of IGF-1 on D407 exposed to SNP insult is mediated by the PI3K/Akt pathway. This proposal may be exploited in the clinic to improve the viability of insulted retinal cells for maintaining physiological vision.

The suprachoroidal pathway: a new drug delivery route to the back of the eye.

The development of safe and convenient drug delivery strategies for treatment of posterior segment eye diseases is challenging. Although intravitreal injection has wide acceptance amongst clinicians, its use is associated with serious side-effects. Recently, the suprachoroidal space (SCS) has attracted the attention of ophthalmologists and pharmaceutical formulators as a potential site for drug administration and delivery to the posterior segment of the eye. This review highlights the major constraints of drug delivery to the posterior eye segment, key anatomical and physiological features of the SCS and drug delivery applications of this route with emphasis on microneedles along with future perspectives.

The nerve growth factor signaling and its potential as therapeutic target for glaucoma.

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.