Learning from people with long-term conditions: new insights for governance in primary health care

Internationally, system-wide changes to the structures and systems governing health care aim to improve outcomes for patients, quality of care and access to services. The introduction of top-down centrally driven solutions to governance of health care, at the same time as increasing policy emphasis on greater ‘bottom up’ patient and public involvement in all aspects of health care, has set up complex tensions for policy implementation and health care practice. This paper explores the interplay of these agendas in the context of changes in primary health care services provided by the National Health Service (NHS) in England. Specifically, it looks at an example of service user involvement in a study (the PEGI study) of professional response to changes in the governance and incentives in the care of people with long-term conditions. This qualitative study was conducted in three Primary Care Trust sites in England. Service users influenced and guided the study throughout. In-depth interviews with 56 health and social care professionals engaged in the development of local policies and the delivery of care for people with complex long-term illness drew on vignettes developed by 32 members from three Service User Reference Groups (SURG). Themes generated by the cross case analysis were validated through these SURG groups. The findings presented here focus on four themes about risk and comparison of professionals’/service users’ perspectives of the issues: managing risks/consistent support, the risks of letting go/feeling in control, professionalism/helping people to help themselves, and managing expectations/professionals losing out. Service user involvement added value by: validating understandings of governance, framing debates to focus on what matters at the point of care, and enabling perspective sharing and interaction. We suggest that more collaborative forms of governance in health care, that take account of service user perspectives and enable interaction with professional groups, could help to validate processes of quality assurance and provide motivation for continuous quality improvement. We offer a model for ‘opening up’ collaborative projects to evaluation and appraisal and a process for critical reflection of the interrelationships between the PEGI study context, researcher issues, methods/approach and outcomes/impact of service user involvement

An Instrumented Walking-Aid to Assess and Retrain Gait

An instrumented walking-aid, the iWA system, has been developed to measure kinematic and kinetic properties of walking aid (WA) use and deliver feedback to improve gait. The clinical requirements, technical specification and design of the system are developed through clinical collaboration. The development of the system is described, including hardware components and data analysis used to process the measured data for assessment. The system measurements are validated under controlled laboratory conditions. The iWA system is evaluated in a typical UK clinical environment by a participant in a rehabilitation session. The resultant data successfully capture the quality of the participant’s walking aid use and agree with clinical opinion, supporting the efficacy of this approach

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Case study in six sigma methadology : manufacturing quality improvement and guidence for managers

This article discusses the successful implementation of Six Sigma methodology in a high precision and critical process in the manufacture of automotive products. The Six Sigma define–measure–analyse–improve–control approach resulted in a reduction of tolerance-related problems and improved the first pass yield from 85% to 99.4%. Data were collected on all possible causes and regression analysis, hypothesis testing, Taguchi methods, classification and regression tree, etc. were used to analyse the data and draw conclusions. Implementation of Six Sigma methodology had a significant financial impact on the profitability of the company. An approximate saving of US$70,000 per annum was reported, which is in addition to the customer-facing benefits of improved quality on returns and sales. The project also had the benefit of allowing the company to learn useful messages that will guide future Six Sigma activities

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Asymptotically Lifshitz wormholes and black holes for Lovelock gravity in vacuum

Static asymptotically Lifshitz wormholes and black holes in vacuum are shown to exist for a class of Lovelock theories in d=2n+1>7 dimensions, selected by requiring that all but one of their n maximally symmetric vacua are AdS of radius l and degenerate. The wormhole geometry is regular everywhere and connects two Lifshitz spacetimes with a nontrivial geometry at the boundary. The dynamical exponent z is determined by the quotient of the curvature radii of the maximally symmetric vacua according to n(z^2-1)+1=(l/L)^2, where L corresponds to the curvature radius of the nondegenerate vacuum. Light signals are able to connect both asymptotic regions in finite time, and the gravitational field pulls towards a fixed surface located at some arbitrary proper distance to the neck. The asymptotically Lifshitz black hole possesses the same dynamical exponent and a fixed Hawking temperature given by T=z/(2^z pi l). Further analytic solutions, including pure Lifshitz spacetimes with a nontrivial geometry at the spacelike boundary, and wormholes that interpolate between asymptotically Lifshitz spacetimes with different dynamical exponents are also found.Comment: 19 pages, 1 figur