Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Epidemiology, clinical and laboratory characteristics of Staphylococcus aureus bacteraemia in a university hospital in UK

There has been a persistent increase in the number of meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia in the UK. This prospective study included 147 episodes of S. aureus bacteraemia in 139 patients over a 14 month period, from 1 November 2001 to 31 December 2002. Eighty-seven (59%) episodes in 84 patients and 60 (41%) in 56 patients were due to MRSA and MSSA, respectively. An intra-vascular device (29, 33%) and a soft-tissue (15, 25%) source were the commonest identifiable foci for bacteraemia in the MRSA and MSSA groups, respectively. Attributable mortality in the MRSA group was higher than the MSSA group (33% vs 16%; P = 0.03) but there was no statistical difference for either attributable (P = 0.35) or crude (P = 0.39) mortality between the two groups, when adjusted for age, respiratory focus and inappropriate antibiotic therapy. A respiratory source (P = 0.02) and inappropriate antibiotic therapy (P = 0.02) were associated with attributable mortality in the MRSA group whereas advanced age was the only risk factor (P = 0.02) in the MSSA group. The present study shows that S. aureus bacteraemia continues to be a serious infection mostly affecting the elderly and emphasizes the need for improved strategy in the control and management of this condition. © 2006 The Hospital Infection Society.

Effects of advanced glycation end-products (AGEs) on retinal pigment epithelial (RPE) cells lysosomal function:implications for age-related macular degeneration (AMD)

Purpose: RPE lysosomal dysfunction is a major contributor to AMD pathogenesis. Controlled activity of a major class of RPE proteinases, the cathepsins, is crucial in maintaining correct lysosomal function. Advanced glycation end-products (AGEs) accumulate in the Bruch’s membrane (BM) with age, impacting critical RPE functions and in turn, contributing to the development of AMD. The aim of this study was to assess the effect of AGEs on lysosomal function by analysing the expression, processing and activity of the cysteine proteinases cathepsins B, L and S, and the aspartic proteinase cathepsin D. Methods: ARPE-19 cells were cultured on AGE-containing BM mimics (matrigel) for 14 days and compared to untreated substrate. Expression levels and intracellular processing of cathepsins B, D, L and S, were assessed by qPCR and immunoblotting of cell lysates. Lysosomal activity was investigated using multiple activity assays specific to each of the analysed cathepsins. Statistical analysis was performed using the Student’s independent T-test. Results: AGE exposure produced a 36% decrease in cathepsin L activity when compared to non-treated controls (p=0.02, n= 3) although no significant changes were observed in protein expression/processing under these conditions. Both the pro and active forms of cathepsin S decreased by 40% (p=0.04) and 74% (p=0.004), respectively (n=3). In contrast, the active form of the cathepsin D increased by 125% (p=0.005, n= 4). However, no changes were observed in the activity levels of both cathepsins S and D. In addition, cathepsin B expression, processing and activity also remained unaltered following AGE exposure. Conclusions: AGEs accumulation in the extracellular matrix, a phenomenon associated with the natural aging process of the BM, attenuates the expression, intracellular processing and activity of specific lysosomal effectors. Altered enzymatic function may impair important lysosomal processes such as endocytosis, autophagy and phagocytosis of photoreceptor outer segments, each of which may influence the age-related dysfunction of the RPE and subsequently, AMD pathogenesis.

The experience of living with age related macular degeneration:A longitudinal study into the impact of age related macular degeneration on quality of life

In this thesis I contribute to the understanding of the experience of living with Age-Related Macular Degeneration (AMD) and its impact on quality of life through the use of a pragmatically guided mixed methods approach. AMD is a condition resulting in the loss of central vision in old age which can have a huge impact on the lives of patients. This thesis includes: literature reviewing; qualitative meta-synthesis; surveys and descriptive statistics; observation; and analysis of in-depth interviewing, in order to build a picture of what it is like for older people to live with AMD. I present the findings from six separate studies each designed to answer specific research questions. I begin with a mixed methods study to determine how well the most commonly used measure of quality of life for AMD patients’ represents patient experiences. I then go on to investigate the experiences of patients with AMD through a meta-synthesis of qualitative research and finally present four of my own empirical studies three of which investigate the experiences of patients with different types of AMD: early dry AMD, treatable wet AMD and advanced wet AMD and the final study investigates what it is like for a couple living together with AMD. Throughout the qualitative studies I use Interpretative Phenomenological Analysis (IPA) to develop an understanding of the experiences and life contexts of patients with AMD. Through rigorous analysis, I identify a range of themes which highlight the shared and divergent experiences of individuals with AMD and the need to acknowledge patients’ past, present and potential future life contexts and experiences when providing services to older people with AMD. I relate the findings of the six studies to the wider psychological literature on chronic illness and make recommendations for services for patients with AMD to be provided holistically within a lifeworld-led health care model.

Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

This study compared the molecular lipidomic profi le of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identifi ed 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profi le in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N -acyltaurines were signifi cantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were signifi cantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identifi ed individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These fi ndings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profi le of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. -Reis, A., A. Rudnitskaya, P. Chariyavilaskul, N. Dhaun, V. Melville, J. Goddard, D. J. Webb, A. R. Pitt, and C. M. Spickett. Topdown lipidomics of low density lipoprotein reveal altered lipid profi les in advanced chronic kidney disease. J. Lipid Res. 2015.