Warfarin use in the elderly: The nurses' perspective

Objective: To explore the barriers to warfarin use from the perspective of nurses working in aged care. Design: A qualitative study, involving a semi-structured group interview, during March-April 2001. Setting and Subjects: Eleven nurses, employed within the catchment of the Northern Sydney Area Health Service, who were involved in the care of elderly warfarinised patients. Main outcome measure: Identification, via thematic analysis, of the main themes underpinning the nursing perspective on warfarin use in this setting, with regard to their perceived role/s, experiences with patients, and potential strategies for managing the therapy. Results: Five main themes were identified: perceived patient attitude toward warfarin; barriers to the use of warfarin; expressed lack of confidence in the processes involved; nurses' role in warfarin use; and strategies to improve warfarin use. Nurses were concerned about warfarin use in the elderly, but felt they had a limited capacity to intervene. Conclusion: Nurses are potentially underutilised as a resource and support for both patients and prescribers, in the management of warfarin therapy

Balancing risk versus benefit: The elderly patient's perspective on warfarin therapy

Warfarin theraphy is underused in the target at-risk elderly population. Clinicians perceive that older patients are reluctant to use this theraphy, however the perspective of patients or their carers has yet to be explored. Objective: To explore in-depth the perspectives of elderly patients and/ or their carers regarding the use of warfarin therapy. Method: A qualitative study, using semi-structured group interviews was undertaken. The audio-taped discussions were transcribed verbatim, then thematically analysed to identify emergent themes. Group discussions were conducted at a major Sydney teaching hospital, over a 2-month period. Individuals aged 65 years or older (and/or their carers) who were using long-term (6 months) warfarin therapy were recruited by voluntary response to study flyers. Results: 17 patients and carers (mean age 77.2 SD=7.5 years) participated in one of two focus groups. Five core themes emerged regarding warfarin therapy: inadequate knowledge and understanding about it, patients/carers variable experience of information provision, cycle of reactions to being on it, issues in its practical management, and the spectrum of experiences with it. Overall, participants were very accepting of the therapy, describing a high level of compliance, despite initial fears and anxieties, and a relative lack of knowledge. Patients felt somewhat abandoned in their management of warfarin due to the lack of ongoing support services in the community, and inadequate information provision. Conclusions: Elderly patients and their carers appear to be quite accepting of warfarin therapy, in contrast to the perceptions of health care professionals. More effort is needed, however, in terms of information provision, particularly in the form of community-based services, to assist patients in the long-term management of warfarin

Management of warfarin in atrial fibrillation: Views of health professionals, older patients and their carers

Objective: To identify the views of health professionals, patients and their carers on strategies to improve the use and management of warfarin in older patients with atrial fibrillation. Design: Qualitative study based on analysis of group interviews. Setting: A major metropolitan teaching hospital, from 1 March to 30 April 2003. Participants: 14 patients (≥ 65 years) with established atrial fibrillation and taking warfarin, three carers, 12 specialists, eight general practitioners, six community pharmacists, nine hospital pharmacists, and 11 nurses volunteered in response to flyers promoting the study. Results: Suggested strategies to improve warfarin management targeted support services for GPs and patients. Hospital-based clinicians felt that dissemination of trial evidence to GPs to support treatment recommendations is required, and that GPs need to enlist allied health professionals in the management of patients taking warfarin. GPs preferred access to practical advice from expert colleagues on the day-to-day management. Patients requested more information about warfarin therapy, as access to information is inadequate, particularly from primary sources (GPs, community pharmacists). Verbal and written information are equally important, but a single counselling session or supply of a booklet was viewed as inadequate. Participants identified various interventions for all levels of warfarin management; from the collective input, a framework for management strategies was developed. Conclusions: Health professionals and patients require more customised information to support warfarin use and management

The dispersion of spherical droplets in source–sink flows and their relevance to the COVID-19 pandemic

In this paper, we investigate the dynamics of spherical droplets in the presence of a source-sink pair flow field. The dynamics of the droplets is governed by the Maxey-Riley equation with Basset-Boussinesq history term neglected. We find that, in the absence of gravity, there are two distinct behaviours for the droplets: small droplets cannot go further than a specific distance, which we determine analytically, from the source before getting pulled into the sink. Larger droplets can travel further from the source before getting pulled into the sink by virtue of their larger inertia, and their maximum travelled distance is determined analytically. We investigate the effects of gravity, and we find that there are three distinct droplet behaviours categorised by their relative sizes: small, intermediate-sized, and large. Counterintuitively, we find that the droplets with minimum horizontal range are neither small nor large, but of intermediate size. Furthermore, we show that in conditions of regular human respiration, these intermediate-sized droplets range in size from a few $\mu$m to a few hundred $\mu$m. The result that such droplets have a very short range could have important implications for the interpretation of existing data on droplet dispersion.Comment: 14 pages, 7 figure

Current and Calcium Responses to Local Activation of Axonal NMDA Receptors in Developing Cerebellar Molecular Layer Interneurons

In developing cerebellar molecular layer interneurons (MLIs), NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs) or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca2+ channels (VDCCs). Using Ca2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg2+ or by the addition of APV. Similar paradigms yielded restricted Ca2+ transients in interneurons loaded with a Ca2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca2+-induced Ca2+ release process mediated by presynaptic Ca2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca2+-mediated synaptic plasticity

Responses to environmental enrichment differ with sex and genotype in a transgenic mouse model of Huntington's disease.

BACKGROUND: Environmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an "enriched" environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The "home cage" and "playground" groups were subdivided into "handling" (stimulated throughout the experimental period) and "no-handling" groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice. CONCLUSIONS/SIGNIFICANCE: We show that even when mice are living in an enriched home cage, further EE had beneficial effects. However, the improvements in cognition and survival vary with sex and genotype. These results indicate that EE may improve the quality of life of HD patients, but we suggest that EE as a therapy should be tailored to individuals

APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

<p>Abstract</p> <p>Background</p> <p>5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets.</p> <p>Methods</p> <p>Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified.</p> <p>Results</p> <p>APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set. Stratified analysis revealed that protein expression of APRIL in the tumour stroma is associated with survival in adjuvant 5FU treated patients only (n = 103, p < 0.001), and is independently predictive of lack of clinical benefit from adjuvant 5FU [HR 6.25 (95%CI 1.48-26.32), p = 0.013].</p> <p>Conclusions</p> <p>A combined investigative model, analysing the transcriptional response in clinical tumour specimens and cancers cell lines, has identified APRIL, a novel chemo-resistance biomarker with independent predictive impact in 5FU-treated CRC patients, that may represent a target for novel therapeutics.</p

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Impact and the reflexive imperative in criminal justice policy, practice and research

This chapter is a substantive editorial introduction to the book, Reflexivity and Criminal Justice: Intersections of Policy, Practice and Research. It develops and argues for an account of reflexivity in criminology beyond the researcher-researched relationship to the field of research itself. Universities are under increasing pressure to document the value of their work, often defined instrumentally in terms of immediate practical and commercial activities. This has led to increasing emphasis on ‘partnerships’ and knowledge exchange with organisations and actors outside of academia. While such relationships may be empowering and supportive of good research and thriving societies, they also raise critical questions about agenda setting and valuation of social science. These questions become especially acute in a discipline such as criminology, with its attention to crime control, surveillance and state punishment, topics which can be co-opted by particular interests. We address the potential and risks of reflexivity in this setting, concluding that it might offer a stance that assists researchers in exposing the complicated dynamics of the conditions of criminal justice research in contemporary times. The content of the chapters comprising the book are summarised and woven into the discussion throughout this introduction