An evaluation of virtual ethics discussion groups as a method of learning on a pharmacist Independent Prescribing (IP) programme.

BACKGROUND AND PURPOSE: A postgraduate body within Queen's University Belfast (QUB) has offered a pharmacist Independent Prescribing (IP) programme to pharmacists living locally in Northern Ireland (NI) since 2006. In 2016, this course was modified and delivered by the School of Pharmacy within QUB for a non-local population of pharmacists from Great Britain (GB). In order to substitute face-to-face, live training in NI, distance learning methods were employed for one of the modules that involved studying ethical dilemmas. The purpose of this study was to assess participant acceptance and perceived effectiveness of the utilized distance learning methods. EDUCATIONAL ACTIVITY AND SETTING: All participants within Cohort 2 of the IP programme offered to GB pharmacists viewed an online recorded lecture on dealing with ethical dilemmas. This involved being taught about a professional decision-making model. Participants then applied this model to four ethical case studies via virtual discussion groups and were invited to complete a questionnaire regarding their views on these teaching methods. FINDINGS: Twenty participants viewed the online recorded lecture, and 19 attended the virtual discussion groups. Eighteen participants (90%) responded to the survey. Participants reacted positively to the e-learning format. Following the training, all participants felt confident applying the professional decision-making model and only one did not intend to apply the model to their practice. SUMMARY: The utilized e-learning format was well received and effective in producing pharmacists who felt confident approaching and resolving ethical dilemmas in their new roles as pharmacist prescribers.

Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice.

Reduced sunlight exposure has been associated with an increased incidence of Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m²) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene performed. UV irradiation of skin was associated with a significant change in the beta-diversity of faeces compared to nonirradiated mice, independently of vitamin D. Specifically, members of phylum Firmicutes, including Coprococcus, were enriched, whereas members of phylum Bacteroidetes, such as Bacteroidales, were depleted. Expression of colonic CYP27B1 increased by four-fold and IL1ß decreased by five-fold, suggesting a UVR-induced anti-inflammatory effect. UV-irradiated mice, however, were not protected against colitis induced by dextran sodium sulfate (DSS), although distinct faecal microbiome differences were documented post-DSS between UV-irradiated and nonirradiated mice. Thus, skin exposure to UVR alters the faecal microbiome, and further investigations to explore the implications of this in health and disease are warranted.

High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis.

Vitamin D has been suggested as a possible adjunctive treatment to ameliorate disease severity in human inflammatory bowel disease. In this study, the effects of diets containing high (D++, 10,000 IU/kg), moderate (D+, 2,280 IU/kg) or no vitamin D (D-) on the severity of dextran sodium sulphate (DSS) colitis in female C57Bl/6 mice were investigated. The group on high dose vitamin D (D++) developed the most severe colitis as measured by blinded endoscopic (p < 0.001) and histologic (p < 0.05) assessment, weight loss (p < 0.001), drop in serum albumin (p = 0.05) and increased expression of colonic TNF-α (p < 0.05). Microbiota analysis of faecal DNA showed that the microbial composition of D++ control mice was more similar to that of DSS mice. Serum 25(OH)D3 levels reduced by 63% in the D++ group and 23% in the D+ group after 6 days of DSS treatment. Thus, high dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis, with a fall in circulating vitamin D occurring as a secondary event in response to the inflammatory process.

"It just made me feel so desolate": Patients' narratives of weight gain following laparoscopic insertion of a gastric band.

AIMS AND OBJECTIVES: To describe the experiences of patients who have failed to maintain weight loss following the insertion of a laparoscopic adjustable gastric band (LAGB) for the treatment of morbid obesity. BACKGROUND: Obesity is a global health problem resulting in physical, psychological and economic problems and presenting challenges for health services. Surgical intervention is an increasingly common approach to treatment; however, some patients do not sustain their weight loss following bariatric surgery and little is known about people's longer-term experiences following LAGB insertion. DESIGN: A narrative-based qualitative interview study. METHODS: A purposive sample of ten participants who had undergone LAGB insertion for morbid obesity was recruited. Semistructured interviews were conducted in 2014. Thematic analysis identified codes and emerging themes common to the participants' experiences. FINDINGS: Three major themes emerged: living with the side effects, regret and lack of support. These reflect the difficulties participants experienced and provide new insights on why weight loss is not sustained after 2 years following surgery. CONCLUSION: Participants reported that the surgery had a detrimental effect on their lives and some regretted having the band inserted. These findings identify areas of care that need to be addressed if patients undergoing LAGB are to experience its potential benefits and indicate that further research is needed into the long-term effects of gastric band insertion. Patients need to be better informed about the consequences of bariatric surgery if it is to have a lasting impact on their weight reduction. RELEVANCE TO CLINICAL PRACTICE: Patients require comprehensive information and support before and after LAGB insertion to develop strategies which will help them lose weight and sustain it over the longer term. Clinicians need to be sensitive to patients' needs when weight loss plateaus or weight is regained and intensify support during these periods.

Prostaglandin E2 and polyenylphosphatidylcholine protect against intestinal fibrosis and regulate myofibroblast function.

BACKGROUND: Intestinal fibrosis is a serious and often recurrent complication of inflammatory bowel disease despite surgical intervention. The anti-fibrotic potential of prostaglandin E2 (PGE2) and polyenylphosphatidylcholine (PC) was investigated using the murine model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic intestinal inflammation and fibrosis, and murine and human intestinal myofibroblasts. METHODS: Mice were treated with TNBS enemas weekly for 2 or 6 weeks ± PGE2 (10 mg/kg/day orally) or PC (200 mg/kg/day orally). Inflammation and fibrosis were histologically assessed and scored. Pro-inflammatory cytokines, TLR4, and ECM-related gene expression from the colonic tissue and cultured myofibroblasts were assessed by RT-qPCR. The levels of α-SMA(+) staining and endogenous PGE2 in vivo were also assessed. RESULTS: Both PGE2 and PC treatment significantly decreased TNBS-induced intestinal inflammation and excess collagen deposition in vivo. This was accompanied by decreased α-SMA(+) staining in the lamina propria and lower collagen type I (COL1α1) expression. Endogenous PGE2 levels demonstrated that PC was not being converted into PGE2, thus mediating its effects primarily via PGE2-independent pathways. Both PGE2 and the PC isoform, 1,2-dilinoleoylphosphatidylcholine (DLPC), regulated primary mouse myofibroblast and CCD-18co COL1α1 production, and induced lower collagen type I to III and TGF-ß1 to TGF-ß3 ratios, demonstrating their ability to induced normal healing in the presence of phorbol 12-myristate 13-acetate (protein kinase C-dependent inducer of collagen production). CONCLUSION: PGE2 and PC both have potent anti-fibrogenic potentials in their ability to regulate inflammatory cell and myofibroblast accumulation within inflamed tissue, to decrease pro-inflammatory cytokine expression and to maintain normal healing in an inflammatory environment.

Secreted protein acidic and rich in cysteine (SPARC) exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis.

BACKGROUND: Secreted Protein Acidic and Rich in Cysteine (SPARC) is expressed during tissue repair and regulates cellular proliferation, migration and cytokine expression. The aim was to determine if SPARC modifies intestinal inflammation. METHODS: Wild-type (WT) and SPARC-null (KO) mice received 3% dextran sodium sulphate (DSS) for 7 days. Inflammation was assessed endoscopically, clinically and histologically. IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-12/IL23p40, TNF-α, IFN-γ, RANTES, MCP-1, MIP-1α, MIP-1ß, MIG and TGF-ß1 levels were measured by ELISA and cytometric bead array. Inflammatory cells were characterised by CD68, Ly6G, F4/80 and CD11b immunofluorescence staining and regulatory T cells from spleen and mesenteric lymph nodes were assessed by flow cytometry. RESULTS: KO mice had less weight loss and diarrhoea with less endoscopic and histological inflammation than WT animals. By day 35, all (n = 13) KO animals completely resolved the inflammation compared to 7 of 14 WT mice (p<0.01). Compared to WTs, KO animals at day 7 had less IL1ß (p= 0.025) and MIG (p = 0.031) with higher TGFß1 (p = 0.017) expression and a greater percentage of FoxP3+ regulatory T cells in the spleen and draining lymph nodes of KO animals (p<0.01). KO mice also had fewer CD68+ and F4/80+ macrophages, Ly6G+ neutrophils and CD11b+ cells infiltrating the inflamed colon. CONCLUSIONS: Compared to WT, SPARC KO mice had less inflammation with fewer inflammatory cells and more regulatory T cells. Together, with increased TGF-ß1 levels, this could aid in the more rapid resolution of inflammation and restoration of the intestinal mucosa suggesting that the presence of SPARC increases intestinal inflammation.

Indomethacin and retinoic acid modify mouse intestinal inflammation and fibrosis: a role for SPARC.

The mouse model of 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced intestinal fibrosis allows for detailed study of the extracellular matrix changes that complicate Crohn's disease. Indomethacin induces intestinal fibrosis, while retinoic acid (RA) reduces liver fibrosis. Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix-modifying agent, may potentially link these opposing effects. Our aim was to determine the effects of indomethacin and RA and to evaluate their correlation to SPARC expression in the TNBS mouse model. CD-1 mice were randomised to TNBS enemas weekly for 2 or 8 weeks with or without indomethacin (0.2 mg/kg per day) or RA (100 microg/kg per day). At 2 weeks, indomethacin/TNBS enhanced and RA reduced inflammation, tissue destruction and fibrosis. The expression of SPARC was inversely related to fibrosis, but not to inflammation, in the TNBS-alone groups at 2 weeks; these differences were lost by 8 weeks. The results demonstrate that indomethacin increases TNBS-induced fibrosis in mice, while RA reduces it, and that SPARC may link these opposing effects.