Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY

Oral cancer awareness of undergraduate medical and dental students

<p>Abstract</p> <p>Background</p> <p>The incidence of oral cancer is increasing in the United Kingdom. Early detection of oral cancers makes them more amenable to treatment and allows the greatest chance of cure. Delay in presentation and/or referral has a significant effect on the associated morbidity and mortality. Lack of general medical practitioner and general dental practitioner oral cancer knowledge has been shown to contribute to delays in referral and treatment. The aim of this study was to investigate the oral cancer awareness of future general medical and general dental practitioners by assessing undergraduate medical and dental students' knowledge of prevention and early detection of oral cancer.</p> <p>Method</p> <p>Questionnaires were delivered to undergraduate medical and dental students at the University of Dundee, assessing oral examination habits, delivery of advice on oral cancer risk factors, knowledge of oral cancer risk factors and clinical appearance, preferred point of referral and requests for further information.</p> <p>Results</p> <p>Undergraduate medical students were less likely to examine patients' oral mucosa routinely and less likely to advise patients about risk factors for oral cancer. Medical students identified fewer oral cancer risk factors. In particular alcohol use was identified poorly. Medical students also identified fewer oral changes associated with oral cancer. Erythroplakia and erythroleukoplakia were identified poorly. Medical students felt less well informed regarding oral cancer. 86% and 92% of undergraduate medical and dental students respectively requested further information about oral cancer.</p> <p>Conclusion</p> <p>This study highlights the need for improved education of undergraduate medical and dental students regarding oral cancer.</p

Study of avidity of antigen-specific antibody as a means of understanding development of long-term immunological memory after Vibrio cholerae O1 infection

The avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) and Vibrio cholerae O1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n = 30), as well as vaccinees (n = 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P < 0.05; Spearman's ρ = 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses to Vibrio cholerae O1 antigens

Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice

BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. CONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota

Patient-, organization-, and system-level barriers and facilitators to preventive oral health care:A convergent mixed-methods study in primary dental care

Background: Dental caries is the most common chronic disease of adult and childhood, a largely preventable yet widespread, costly public health problem. This study identified patient-, organization-, and system-level factors influencing routine delivery of recommended care for prevention and management of caries in primary dental care. Methods: A convergent mixed-methods design assessed six guidance-recommended behaviours to prevent and manage caries (recording risk, risk-based recall intervals, applying fluoride varnish, placing preventive fissure sealants, demonstrating oral health maintenance, taking dental x-rays). A diagnostic questionnaire assessing current practice, beliefs, and practice characteristics was sent to a random sample of 651 dentists in National Health Service (NHS) Scotland. Eight in-depth case studies comprising observation of routine dental visits and dental team member interviews were conducted. Patient feedback was collected from adult patients with recent checkups at case study practices. Key informant interviews were conducted with decision makers in policy, funding, education, and regulation. The Theoretical Domains Framework within the Behaviour Change Wheel was used to identify and describe patient-, organization-, and system-level barriers and facilitators to care. Findings were merged into a matrix describing theoretical domains salient to each behaviour. The matrix and Behaviour Change Wheel were used to prioritize behaviours for change and plan relevant intervention strategies. Results: Theoretical domains associated with best practice were identified from the questionnaire (N-196), case studies (N = 8 practices, 29 interviews), and patient feedback (N = 19). Using the study matrix, key stakeholders identified priority behaviours (use of preventive fissure sealants among 6–12-year-olds) and strategies (audit and feedback, patient informational campaign) to improve guidance implementation. Proposed strategies were assessed as appropriate for immediate implementation and suitable for development with remaining behaviours. Conclusions: Specific, theoretically based, testable interventions to improve caries prevention and management were coproduced by patient-, practice-, and policy-level stakeholders. Findings emphasize duality of behavioural determinants as barriers and facilitators, patient influence on preventive care delivery, and benefits of integrating multi-level interests when planning interventions in a dynamic, resource-constrained environment. Interventions identified in this study are actively being used to support ongoing implementation initiatives including guidance, professional development, and oral health promotion

Size-Frequency Distributions along a Latitudinal Gradient in Middle Permian Fusulinoideans

Geographic gradients in body size within and among living species are commonly used to identify controls on the long-term evolution of organism size. However, the persistence of these gradients over evolutionary time remains largely unknown because ancient biogeographic variation in organism size is poorly documented. Middle Permian fusulinoidean foraminifera are ideal for investigating the temporal persistence of geographic gradients in organism size because they were diverse and abundant along a broad range of paleo-latitudes during this interval (∼275–260 million years ago). In this study, we determined the sizes of Middle Permian fusulinoidean fossils from three different paleo-latitudinal zones in order to examine the relationship between the size of foraminifers and regional environment. We recovered the following results: keriothecal fusulinoideans are substantially larger than nonkeriothecal fusulinoideans; fusulinoideans from the equatorial zone are typically larger than those from the north and south transitional zones; neoschwagerinid specimens within a single species are generally larger in the equatorial zone than those in both transitional zones; and the nonkeriothecal fusulinoideans Staffellidae and Schubertellidae have smaller size in the north transitional zone. Fusulinoidean foraminifers differ from most other marine taxa in exhibiting larger sizes closer to the equator, contrary to Bergmann's rule. Meridional variation in seasonality, water temperature, nutrient availability, and carbonate saturation level are all likely to have favored or enabled larger sizes in equatorial regions. Temporal variation in atmospheric oxygen concentrations have been shown to account for temporal variation in fusulinoidean size during Carboniferous and Permian time, but oxygen availability appears unlikely to explain biogeographic variation in fusulinoidean sizes, because dissolved oxygen concentrations in seawater typically increase away from the equator due to declining seawater temperatures. Consequently, our findings highlight the fact that spatial gradients in organism size are not always controlled by the same factors that govern temporal trends within the same clade

Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

BACKGROUND: Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. METHODOLOGY/PRINCIPAL FINDINGS: Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. CONCLUSIONS/SIGNIFICANCE: Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- ) and mature (CD3+) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection