Simplifying medication regimens for residents of aged care facilities: Pharmacist and physician use of a structured five-step medication simplification tool.

BACKGROUND: Pharmacist-led medication regimen simplification using a structured approach can reduce unnecessary medication regimen complexity in residential aged care facilities (RACFs), but no studies have investigated simplification by different health professionals, nor the extent to which simplification is recommended during comprehensive medication reviews. OBJECTIVES: To compare medication regimen simplification opportunities identified by pharmacists, general medical practitioners (GPs), and geriatricians and to determine if pharmacists identified simplification opportunities during routinely conducted comprehensive medication reviews in RACFs for these same residents. METHODS: Three pharmacists, three GPs and three geriatricians independently applied the Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) to medication data for 83 residents taking medications at least twice daily. Interrater agreement was calculated using Fleiss's kappa. Pharmacist medication review reports for the same 83 residents were then examined to identify if the pharmacists conducting these reviews had recommended any of the simplification strategies. RESULTS: Overall, 77 residents (92.8 %) taking medications at least twice daily could have their medication regimen simplified by at least one health professional. Pharmacists independently simplified 53.0-77.1 % of medication regimens (Κ = 0.60, 95%CI 0.46-0.75, indicating substantial agreement), while GPs simplified 74.7-89.2 % (Κ = 0.44, 95%CI 0.24-0.64, moderate agreement) and geriatricians simplified 41.0-66.3 % (Κ = 0.30, 95%CI 0.16-0.44, fair agreement). No simplification recommendations were included in the reports previously prepared by pharmacists as part of the comprehensive medication reviews undertaken for these residents. CONCLUSION: Pharmacists, GPs, and geriatricians can all identify medication regimen simplification opportunities, although these opportunities differ within and between professional groups. Although opportunities to simplify medication regimens during comprehensive medication reviews exist, simplification is not currently routinely recommended by pharmacists performing these reviews in Australian RACFs.

Therapeutic Potential of a Novel Vitamin D3 Oxime Analogue, VD1-6, with CYP24A1 Enzyme Inhibitory Activity and Negligible Vitamin D Receptor Binding.

The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. CYP24A1 hydroxylates both 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is the first step of vitamin D catabolism. An abnormal status of the upregulation of CYP24A1 occurs in many diseases, including chronic kidney disease (CKD). CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. Previous studies have indicated that CYP24A1 inhibition may be an effective strategy to increase endogenous vitamin D activity and decrease SHPT. This study has designed and synthesized a novel C-24 O-methyloxime analogue of vitamin D3 (VD1-6) to have specific CYP24A1 inhibitory properties. VD1-6 did not bind to the vitamin D receptor (VDR) in concentrations up to 10-7 M, assessed by a VDR binding assay. The absence of VDR binding by VD1-6 was confirmed in human embryonic kidney HEK293T cultures through the lack of CYP24A1 induction. However, in silico docking experiments demonstrated that VD1-6 was predicted to have superior binding to CYP24A1, when compared to that of 1,25(OH)2D3. The inhibition of CYP24A1 by VD1-6 was also evident by the synergistic potentiation of 1,25(OH)2D3-mediated transcription and reduced 1,25(OH)2D3 catabolism over 24 h. A further indication of CYP24A1 inhibition by VD1-6 was the reduced accumulation of the 24,25(OH)D3, the first metabolite of 25(OH)D catabolism by CYP24A1. Our findings suggest the potent CYP24A1 inhibitory properties of VD1-6 and its potential for testing as an alternative therapeutic candidate for treating SHPT.

New therapeutic strategies for combatting gastrointestinal toxicity.

PURPOSE OF REVIEW: An overwhelming majority of chemotherapy agents are known to cause gastrointestinal mucositis, an unwanted side effect of cancer treatment, for which no effective treatment currently exists. The pathological processes underlying the development of gastrointestinal mucositis are many and varied, with multiple pathways thought to be involved in initiation of inflammation and apoptosis. Physiological and or biochemical-based deficiencies, such as vitamin D deficiency and gut microbiome density and population, are also thought to have an impact on mucositis severity. RECENT FINDINGS: Recent studies investigating inflammatory pathways, such as cytokines and apoptotic markers, do show that interleukin-blocking proteins alleviate symptoms of gastrointestinal mucositis. However, the effectiveness of these treatments varies depending on the type of anticancer agent administered, meaning blocking compounds may be limited in their application. Targeting the host's gut microbiome in preventing dysbiosis is also thought to be a potential avenue for exploration. The use of probiotic gut bacteria (i.e. Lactobacillus spp.), while beneficial in preventing chemotherapy radiotherapy-induced diarrhoea, does not seem to alleviate the physiological damage caused by gastrointestinal mucositis. Vitamin D has been widely shown to have a host of anti-inflammatory and immunomodulatory effects in the intestine, as well as anticancer properties and therefore, may reduce severity of gastrointestinal mucositis. SUMMARY: While anti-inflammatory and antiapoptotic agents have shown promise in animal models of gastrointestinal mucositis, there is still no singular mechanism allowing for the development of a therapeutic drug to prevent or cure gastrointestinal injury. A greater insight into the exact mechanistic actions of both probiotics and vitamin D might reveal how to improve their use as therapeutic treatments for gastrointestinal mucositis.