Abstract Objectives Most patients receive systemic anticancer therapy (SACT) as day cases and toxicities, if they occur, are likely to appear first in primary care. Pharmaceutical care can be delivered by community pharmacists, but little is known about the epidemiology of SACT toxicities in the community and potential interventions to address these which raise the following questions: what are the typologies of SACT-associated toxicities experienced by community-based patients and what are the associated pharmaceutical care issues (PCIs)? The aim of this study was to identify toxicities and pharmaceutical care issues of patients prescribed SACT for lung cancer and understand the potential for community pharmacists to deliver aspects of cancer care including toxicity management. Methods Retrospective analysis of clinical records of patients prescribed oral and parenteral SACT in 2013–14, to describe patient characteristics; SACT toxicity; PCIs and episodes of unscheduled care. Key findings Twelve categories of toxicity and 13 categories of PCIs were identified from 50 patients. More PCIs were observed with oral SACT/oral-parenteral combinations than with parenteral regimens. The PCIs which could be managed by community pharmacists were mucositis; skin toxicity; gastrointestinal toxicity; reinforcing patient education and identification/prevention of drug interactions. Conclusions Community pharmacists are ideally placed to provide pharmaceutical care to patients with lung cancer prescribed SACT. Cancer specialists in secondary care can signpost patients to community pharmacists for early management of low-grade SACT toxicity.
Drug-eluting stents have been successful in reducing in-stent restenosis but are not suitable for all lesion types and have been implicated in causing late stent thrombosis due to incomplete regeneration of the endothelial cell layer. In this study we implanted stents coated with cicaprost, a prostacyclin analogue with a long plasma half-life and antiproliferative effects on vascular smooth muscle cells, into the iliac arteries of rabbits. At 28-day follow-up we compared neointima formation within the stented vessels and vascular function in adjacent vessels, to assess if cicaprost could reduce restenosis without impairing vessel function. Arteries implanted with cicaprost eluting stents had significantly more neointima compared to bare metal stents. In adjacent segments of artery, endothelium-dependent relaxation was impaired by the cicaprost-eluting stent but vasodilation to an endothelium-independent vasodilator was maintained. We conclude that the presence of the polymer and sub-optimal release of cicaprost from the stent may be responsible for the increased neointma and impaired functional recovery of the endothelium observed. Further experiments should be aimed at optimising release of cicaprost and exploring different stent polymer coatings.
Polydopamine has been found to be a biocompatible polymer capable of supporting cell growth and attachment, and to have antibacterial and antifouling properties. Together with its ease of manufacture and application, it ought to make an ideal biomaterial and function well as a coating for implants. In this paper, atomic force microscope was used to measure the adhesive forces between polymer-, protein- or polydopamine-coated surfaces and a silicon nitride or polydopamine-functionalised probes. Surfaces were further characterised by contact angle goniometry, and solutions by circular dichroism. Polydopamine was further characterised with infrared spectroscopy and Raman spectroscopy. It was found that polydopamine functionalisation of the atomic force microscope probe significantly reduced adhesion to all tested surfaces. For example, adhesion to mica fell from 0.27 ± 0.7 to 0.05 ± 0.01 nN nm
ObjectivesPrevious studies have reported the ability of several phospholipid analogues to successfully inhibit the growth of Acanthamoeba species in vitro. This study tests further phospholipid analogues, either as free drug or in liposomal formulations, and unlike previous studies, examines their comparative toxicities to mammalian cells.
Background Crohn’s disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel (IBD) conditions that result in fluctuations of disease activity. Infliximab and Adalimumab are well-established agents associated with inducing and maintaining remission in IBD. Long term use of this agent has an associated risk profile and significant healthcare budget implications. Aims The aim was to identify patients in remission suitable for discontinuation of anti-TNF therapy and follow their clinical course to identify the patients who maintained a clinical remission Methods A single centre retrospective of our 1000 IBD patients. We reviewed IBD cohort on Anti TNF therapy. Analysis of colonoscopy findings and patient symptoms at time of discontinuation was performed and subsequent clinical follow following withdrawal of therapy. Results We identified 65 patients on Infliximab. 37 (57%) have UC and 28 (43%) have CD. Following a mean treatment interval of 41 months Infliximab therapy was discontinued in 19 (29%) patients. Of the discontinuation cohort 11 (58%) patients had UC, 6 (31.5%) had CD 2 (10.5%) were indeterminate colitis. During a follow up of 36 months 18 (95%) remained in clinical remission, while 1 (5%) relapsed. We identified 198 patients on Adalimumab in our cohort for treatment of CD. Of this cohort 3 (1.5%) were discontinued as they were in clinical remission. The follow up for this arm was 50 months. There have been 2 (66%) relapses in this group. Conclusions Successful remission was achieved in 95% of our Infliximab cohort and 33% of our Adalimumab cohort resulting in fewer hospital admissions, improvement in patient quality of life and decreased healthcare costs that are associated with provision of both maintenance and rescue therapy for flares of disease.
Vaginally administered nitric oxide donors such as isosorbide mononitrate have been used to ripen the uterine cervix in pregnancy. The pharmacokinetics of isosorbide mononitrate following vaginal administration are unknown. Serum levels of isosorbide mononitrate were determined at baseline and 60, 180 and 360 minutes after vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women scheduled for induction of labour at term. Serum levels of isosorbide mononitrate continued to rise up to 360 minutes after isosorbide mononitrate insertion, with mean (SD) final levels of 337 (94) microg/L following isosorbide mononitrate 40 mg and 144 (47) microg/L following isosorbide mononitrate 20 mg, P < 0.01.
INTRODUCTION:
The rising popularity of ultramarathon running over the past few years has seen non-professional runners striving for bigger and tougher extreme physical challenges. Understanding the effects of ultramarathon events and the ultramarathon runners profile provides a unique model to investigate the physiological responses to prolonged physical exertion. The current study determined the metabolic changes induced by extreme exercise through ultra-marathon running in order gain an insight into how metabolism is adapted for endurance performance. Plasma samples were analysed for their metabolomic profiles to determine the metabolic changes. The aim of the current study was to analyse the change in metabolic profile of trained ultramarathon runners in response to an 80.5km simulated treadmill ultramarathon.
METHODS:
Metabolomic profiling of nine trained male ultramarathon runners was performed in response to an 80.5km self-paced treadmill-based time trial performed in a controlled laboratory environment. Plasma samples were obtained from venous whole blood, collected at rest, half-way (40.25km) and on completion of 80.5km (post-80.5km). Samples were analysed by high resolution mass spectrometry in combination with both hydrophilic interaction (HILIC) and reversed phase (RP) chromatography. The extracted putatively identified features were modelled using Simca P 14.1 software.
RESULTS:
The runners completed the distance in 09:00:18±01:14:07 (hh:mm:ss), at a running velocity of 9.8±1.3 km.h-1. The exercise induced a large number of metabolic changes with multiple amino acids decreasing in abundance while there were increases in the levels of a number of acylcarnitines, fatty acids and oxidised fatty acids. There were no significant differences observed between the halfway (40.25km) and post-80.5km samples (p>0.05). A large number of amino acids decreased and fatty acid metabolism was affected with an increase in the formation of medium-chain unsaturated and partially oxidised fatty acids and conjugates of fatty acids with carnitines.
CONCLUSION:
A marked elevation in acylcarnitine levels suggests a source of energy for export into the musculoskeletal mitochondria. The fall in the amino acids used in protein biosynthesis may be due to an increase in protein biosynthesis during exercise. Elevation of oxidised fatty acids may be associated with potent effects on blood vessels promoting either vasodilation or vasoconstriction or as markers of oxidative stress. The pattern of fatty acids and carnitines observed in the current study suggests a large increase in peroxisomal metabolism providing acetyl carnitine as a fuel source. This is the first study to provide evidence of the metabolic profile in response to prolonged ultramarathon running using an untargeted approach. The findings provide an insight into the effects of ultramarathon running on the metabolic specificities and alterations that may demonstrate cardio-protective effects.
In general, there are only a few vaccines administered via mucosal routes, as the mucosal immune system presents numerous hurdles, including diversity in mucosal surface structure, complexity in immune cell interaction and limitations in experimental methodology. This therefore necessitates a range of strategies to be used for each target area. With reference to the three main routes of delivery and associated mucosal surfaces (oral/intestinal, nasal/respiratory and female genital tract), this review examines how coadministration of immune-stimulatory molecules, adjuvants, delivery systems and mucoadhesives are used to improve mucosal vaccine efficacy. Key considerations to the development of next-generation mucosal vaccines include improved efficacy and safety, technological advancements in medical devices to enable convenience and better administration, as well as reduced manufacturing costs.
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