Addressing potentially inappropriate prescribing in older patients: development and pilot study of an intervention in primary care (the OPTI-SCRIPT study)

Background: Potentially inappropriate prescribing (PIP) in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. The prevalence of PIP in Ireland is estimated at 36% with an associated expenditure of over [euro sign]45 million in 2007. The aim of this paper is to describe the application of the Medical Research Council (MRC) framework to the development of an intervention to decrease PIP in Irish primary care.

Methods: The MRC framework for the design and evaluation of complex interventions guided the development of the study intervention. In the development stage, literature was reviewed and combined with information obtained from experts in the field using a consensus based methodology and patient cases to define the main components of the intervention. In the pilot stage, five GPs tested the proposed intervention. Qualitative interviews were conducted with the GPs to inform the development and implementation of the intervention for the main randomised controlled trial.

Results: The literature review identified PIP criteria for inclusion in the study and two initial intervention components - academic detailing and medicines review supported by therapeutic treatment algorithms. Through patient case studies and a focus group with a group of 8 GPs, these components were refined and a third component of the intervention identified - patient information leaflets. The intervention was tested in a pilot study. In total, eight medicine reviews were conducted across five GP practices. These reviews addressed ten instances of PIP, nine of which were addressed in the form of either a dose reduction or a discontinuation of a targeted medication. Qualitative interviews highlighted that GPs were receptive to the intervention but patient preference and time needed both to prepare for and conduct the medicines review, emerged as potential barriers. Findings from the pilot study allowed further refinement to produce the finalised intervention of academic detailing with a pharmacist, medicines review with web-based therapeutic treatment algorithms and tailored patient information leaflets.

Conclusions: The MRC framework was used in the development of the OPTI-SCRIPT intervention to decrease the level of PIP in primary care in Ireland. Its application ensured that the intervention was developed using the best available evidence, was acceptable to GPs and feasible to deliver in the clinical setting. The effectiveness of this intervention is currently being tested in a pragmatic cluster randomised controlled trial.

Trial registration: Current controlled trials ISRCTN41694007.© 2013 Clyne et al.; licensee BioMed Central Ltd.

Invited review - genetic and epigenetic factors influencing CKD

Chronic kidney disease (CKD) has become a serious public health problem because of its associated morbidity, premature mortality and attendant healthcare costs. The rising number of persons with CKD is linked with ageing population structure and an increased prevalence of diabetes, hypertension and obesity. There is an inherited risk associated with developing CKD as evidenced by familial clustering and differing prevalence rates across ethnic groups. Earlier studies to determine the inherited risk factors for CKD rarely identified genetic variants that were robustly replicated. However, improvements in genotyping technologies and analytical methods are now helping to identify promising genetic loci aided by international collaboration and multi-consortia efforts. More recently, epigenetic modifications have been proposed to play a role in both the inherited susceptibility to CKD and, importantly, to explain how the environment dynamically interacts with the genome to alter an individual's disease risk. Genome-wide, epigenome-wide and whole transcriptome studies have been performed and optimal approaches for integrative analysis are being developed. This review summarises recent research and the current status of genetic and epigenetic risk factors influencing CKD using population-based information.

Inhuman and Degrading Punishment, Dignity, and the Limits of Retribution

The recent judgment of the Grand Chamber of the European Court of Human Rights (ECtHR) in Vinter and others v United Kingdom provides a much needed clarification of the parameters of the prohibition on inhuman and degrading punishment under Article 3 of the European Convention on Human Rights (ECHR) as it applies to whole life orders of imprisonment under mandatory life sentences – essentially, life imprisonment without parole. The Grand Chamber’s judgment refines Strasbourg doctrine on life imprisonment and the prospect of release and illuminates key principles concerning inhuman and degrading punishment under Article 3 of the ECHR. This article considers the judgment’s profound significance in relation to both human rights and penology.

Multimodal functional and anatomical imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

Structural and functional change in the microcirculation in type 1 diabetes mellitus predicts future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track change in ocular hemodynamics in patients with this disease. 24 patients with uncomplicated type 1 diabetes mellitus, and 18 age-and-sex matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries and digital photography to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and following inhalation of 100% oxygen. Frequency data was compared between groups. No significant differences were found in the resistive index between groups at baseline or following inhaled oxygen. Frequency analysis of the Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and controls in data captured from the ophthalmic artery (p<0.01 for each band). In response to inhaled oxygen, changes in the frequency band amplitudes were significantly greater in control subjects compared with patients (p<0.05). Only control subjects demonstrated a positive correlation (R=0.61) between change in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical change in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.

Finding the Most Descriptive Substructures in Graphs with Discrete and Numeric Labels

Many graph datasets are labelled with discrete and numeric attributes. Most frequent substructure discovery algorithms ignore numeric attributes; in this paper we show how they can be used to improve search performance and discrimination. Our thesis is that the most descriptive substructures are those which are normative both in terms of their structure and in terms of their numeric values. We explore the relationship between graph structure and the distribution of attribute values and propose an outlier-detection step, which is used as a constraint during substructure discovery. By pruning anomalous vertices and edges, more weight is given to the most descriptive substructures. Our method is applicable to multi-dimensional numeric attributes; we outline how it can be extended for high-dimensional data. We support our findings with experiments on transaction graphs and single large graphs from the domains of physical building security and digital forensics, measuring the effect on runtime, memory requirements and coverage of discovered patterns, relative to the unconstrained approach.

Falls prevention and support:: translating research, integrating services and promoting the contribution of service users for quality and innovative programmes of care

Falls are a significant threat to the safety, health and independence of older citizens. Despite the substantial evidence that is available around effective falls prevention programmes and interventions, their translation into falls reduction programmes and policies has yet to be fully realised. While hip fracture rates are decreasing, the number and incidence of fall-related hospital admissions among older people continue to rise. Given the demographic trends that highlight increasing numbers of older people in the UK, which is broadly reflected internationally, there is a financial and social imperative to minimise the rate of falls and associated injuries. Falling is closely aligned to growing older (Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010). According to the World Health Organization, around 30% of older people aged over 65 and 50% of those over 80 will fall each year (Falls Fact Sheet Number 344, WHO, Geneva, 2010). Falls happen as a result of many reasons and can have harmful consequences, including loss of mobility and independence, confidence and in many cases even death (Cochrane Database Syst Rev 15, 2009, 146; Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010; Falling Standards, Broken Promises: Report of the National
Audit of Falls and Bone Health in Older People 2010, Health Care Quality
Improvement Partnership, London, 2011). What is neither fair nor correct is the
common belief by old and young alike that falls are just another inconvenience to put up with. The available evidence justifiably supports the view that well-organised services, based upon national standards and expert guidance, can prevent future falls among older people and reduce death and disability from fractures. This paper will draw from the UK, as an exemplar for policy and practice, to discuss the strategic direction of falls prevention programmes for older people and the partnerships that need to exist between researchers, service providers and users of services to translate evidence to the clinical setting. Second, it will propose some mechanisms for disseminating evidence to healthcare professionals and other stakeholders, to improve the quality and capacity of the clinical workforce.

A comparison of two informative SNP-based strategies for typing Pseudomonas aeruginosa isolates from patients with cystic fibrosis

BACKGROUND: Molecular typing is integral for identifying Pseudomonas aeruginosa strains that may be shared between patients with cystic fibrosis (CF). We conducted a side-by-side comparison of two P. aeruginosa genotyping methods utilising informative-single nucleotide polymorphism (SNP) methods; one targeting 10 P. aeruginosa SNPs and using real-time polymerase chain reaction technology (HRM10SNP) and the other targeting 20 SNPs and based on the Sequenom MassARRAY platform (iPLEX20SNP).

METHODS: An in-silico analysis of the 20 SNPs used for the iPLEX20SNP method was initially conducted using sequence type (ST) data on the P. aeruginosa PubMLST website. A total of 506 clinical isolates collected from patients attending 11 CF centres throughout Australia were then tested by both the HRM10SNP and iPLEX20SNP assays. Type-ability and discriminatory power of the methods, as well as their ability to identify commonly shared P. aeruginosa strains, were compared.

RESULTS: The in-silico analyses showed that the 1401 STs available on the PubMLST website could be divided into 927 different 20-SNP profiles (D-value = 0.999), and that most STs of national or international importance in CF could be distinguished either individually or as belonging to closely related single- or double-locus variant groups. When applied to the 506 clinical isolates, the iPLEX20SNP provided better discrimination over the HRM10SNP method with 147 different 20-SNP and 92 different 10-SNP profiles observed, respectively. For detecting the three most commonly shared Australian P. aeruginosa strains AUST-01, AUST-02 and AUST-06, the two methods were in agreement for 80/81 (98.8%), 48/49 (97.8%) and 11/12 (91.7%) isolates, respectively.

CONCLUSIONS: The iPLEX20SNP is a superior new method for broader SNP-based MLST-style investigations of P. aeruginosa. However, because of convenience and availability, the HRM10SNP method remains better suited for clinical microbiology laboratories that only utilise real-time PCR technology and where the main interest is detection of the most highly-prevalent P. aeruginosa CF strains within Australian clinics.

The solvable Lie group N_{6, 28}: an example of an almost C_0(\mathcal{K})-C*-algebra

Motivated by the description of the C*-algebra of the affine automorphism group N6,28 of the Siegel upper half-plane of degree 2 as an algebra of operator fields defined over the unitary dual View the MathML source of the group, we introduce a family of C*-algebras, which we call almost C0(K), and we show that the C*-algebra of the group N6,28 belongs to this class.

Laboratizing the border: The production, translation and anticipation of security technologies

This paper critically interrogates how borders are produced by scientists, engineers and security experts in advance of the actual deployment of technical devices they develop. This paper explores the prior stages of translation and decision-making as a socio-technical device is conceived and developed. Drawing on in-depth interviews, observations and ethnographic research of the EU-funded Handhold project (consisting of nine teams in five countries), it explores how assumptions about the way security technologies will and should perform at the border shape the way that scientists, engineers, and security experts develop a portable, integrated device to detect CBRNE threats at borders. In disaggregating the moments of sovereign decision making across multiple sites and times, this paper questions the supposed linearity of how science comes out of and feeds back into the world of border security. An interrogation of competing assumptions and understandings of security threats and needs, of competing logics of innovation and pragmatism, of the demands of differentiated temporalities in detection and interrogation, and of the presumed capacities, behaviours, and needs of phantasmic competitors and end-users reveals a complex, circulating and co-constitutive process of device development that laboratises the border itself. We trace how sovereign decisions are enacted as assemblages in the antecedent register of device development itself through the everyday decisions of researchers in the laboratory, and the material components of the Handhold device itself.

Neuromusculature of Gyrodactylus rysavyi, a monogenean gill and skin parasite of the catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry in conjunction with confocal scanning laser microscopy were used for the first time to describe the nervous and muscle systems of the viviparous monogenean parasite, Gyrodactylus rysavyi inhabiting the gills and skin of the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The musculature of the pharynx, intestine, reproductive tract and the most prominent muscles of the haptor were also described. Two characteristic muscular pads were found lying in the anterior region of the haptor in close contact with the hamuli. To each one of these pads, a group of ventral extrinsic muscles was connected. The role of this ventral extrinsic muscle in the body movement was discussed. The mechanism operating the marginal hooklets was also discussed. The central nervous system (CNS) consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. The CNS is better developed ventrally than dorsally or laterally and it has the highest reactivity for all neuroactive substances examined. Both the central and the peripheral nervous system (PNS) are bilaterally symmetrical. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were explained. The results implicated acetylcholine, FMRFamide-related peptides (FaRPs) and serotonin in sensory and motor function. The results were compared with those of the monogeneans Macrogyrodactylus clarii and M. congolensis inhabiting the gills and skin respectively of the same host fish C. gariepinus.