Quality indicators for the primary care of osteoarthritis: a systematic review.

OBJECTIVE: To identify valid and feasible quality indicators for the primary care of osteoarthritis (OA). DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Electronic reference databases (MEDLINE, EMBASE, CINAHL, HMIC, PsychINFO), quality indicator repositories, subject experts. ELIGIBILITY CRITERIA: Eligible articles referred to adults with OA, focused on development or implementation of quality indicators, and relevant to UK primary care. An English language restriction was used. The date range for the search was January 2000 to August 2013. The majority of OA management guidance has been published within this time frame. DATA EXTRACTION: Relevant studies were quality assessed using previous quality indicator methodology. Two reviewers independently extracted data. Articles were assessed through the Outcome Measures in Rheumatology filter; indicators were mapped to management guidance for OA in adults. A narrative synthesis was used to combine the indicators within themes. RESULTS: 10,853 articles were identified from the search; 32 were included in the review. Fifteen indicators were considered valid and feasible for implementation in primary care; these related to assessment non-pharmacological and pharmacological management. Another 10 indicators were considered less feasible, in various aspects of assessment and management. A small number of recommendations had no published corresponding quality indicator, such as use of topical non-steroidal anti-inflammatory drugs. No negative ('do not do') indicators were identified. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There are well-developed, feasible indicators of quality of care for OA which could be implemented in primary care. Their use would assist the audit and quality improvement for this common and frequently disabling condition.

Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis.

Osteoarthritis (OA) is a leading cause of pain and disability and leads to a reduced quality of life. The aim was to determine the current evidence on risk factors for onset of knee pain/OA in those aged 50 and over. A systematic review and meta-analysis was conducted of cohort studies for risk factors for the onset of knee pain. Two authors screened abstracts and papers and completed data extraction. Where possible, pooled odds ratios (OR) were calculated via random effects meta-analysis and population attributable fractions (PAFs) derived. 6554 papers were identified and after screening 46 studies were included. The main factors associated with onset of knee pain were being overweight (pooled OR 1.98, 95% confidence intervals (CI) 1.57-2.20), obesity (pooled OR 2.66 95% CI 2.15-3.28), female gender (pooled OR 1.68, 95% CI 1.37-2.07), previous knee injury (pooled OR 2.83, 95% CI 1.91-4.19). Hand OA (pooled OR 1.30, 95% CI 0.90-1.87) was found to be non-significant. Smoking was found not to be a statistically significant risk or protective factor (pooled OR 0.92, 95% CI 0.83-1.01). PAFs indicated that in patients with new onset of knee pain 5.1% of cases were due to previous knee injury and 24.6% related to being overweight or obese. Clinicians can use the identified risk factors to identify and manage patients at risk of developing or increasing knee pain. Obesity in particular needs to be a major target for prevention of development of knee pain. More research is needed into a number of potential risk factors.

Epidemic dynamics revealed in dengue evolution.

Dengue is an emerging tropical disease infecting tens of millions of people annually. A febrile illness with potentially severe hemorrhagic manifestations, dengue is caused by mosquito-borne viruses (DENV-1 to -4) that are maintained in endemic transmission in large urban centers of the tropics with periodic epidemic cycles at 3- to 5-year intervals. Puerto Rico (PR), a major population center in the Caribbean, has experienced increasingly severe epidemics since multiple dengue serotypes were introduced beginning in the late 1970s. We document the phylodynamics of DENV-4 between 1981 and 1998, a period of dramatic ecological expansion during which evolutionary change also occurs. The timescale of viral evolution is sufficiently short that viral transmission dynamics can be elucidated from genetic diversity data. Specifically, by combining virus sequence data with confirmed case counts in PR over these two decades, we show that the pattern of cyclic epidemics is strongly correlated with coalescent estimates of effective population size that have been estimated from sampled virus sequences using Bayesian Markov Chain Monte Carlo methods. Thus, we show that the observed epidemiologic dynamics are correlated with similar fluctuations in diversity, including severe interepidemic reductions in genetic diversity compatible with population bottlenecks that may greatly impact DENV evolutionary dynamics. Mean effective population sizes based on genetic data appear to increase prior to isolation counts, suggesting a potential bias in the latter and justifying more active surveillance of DENV activity. Our analysis explicitly integrates epidemiologic and sequence data in a joint model that could be used to further explore transmission models of infectious disease.

Mosquito vectors of West Nile virus during an epizootic outbreak in Puerto Rico.

The purpose of this investigation was to identify the mosquito (Diptera: Culicidae) vectors of West Nile virus (WNV; family Flaviviridae, genus Flavivirus) during an epizootic WNV outbreak in eastern Puerto Rico in 2007. In June 2006, 12 sentinel chicken pens with five chickens per pen were deployed in six types of habitats: herbaceous wetlands, mangrove forests, deciduous forests, evergreen forests, rural areas, and urban areas. Once WNV seroconversion in chickens was detected in June 2007, we began trapping mosquitoes using Centers for Disease Control and Prevention (CDC) miniature (light/CO2-baited) traps, CMT-20 collapsible mosquito (CO2- and ISCA SkinLure-baited) traps, and CDC gravid (hay infusion-baited) traps. We placed the CDC miniature traps both 2-4 m and >30 m from the chicken pens, the collapsible traps 2-4 m from the pens, and the gravid traps in backyards of houses with sentinel chicken pens and in a wetland adjacent to an urban area. We found numerous blood-engorged mosquitoes in the traps nearest to the sentinel chickens and reasoned that any such mosquitoes with a disseminated WNV infection likely served as vectors for the transmission of WNV to the sentinels. We used reverse transcriptase-polymerase chain reaction and isolation (C636) on pools of heads, thoraxes/ abdomens, and legs of collected blood-engorged mosquitoes to determine whether the mosquitoes carried WNV. We detected WNV-disseminated infections in and obtained WNV isolates from Culex nigripalpus Theo (minimum infection rate [MIR] 1.1-9.7/1,000), Culex bahamensis Dyar and Knab (MIR 1.8-6.0/1,000), and Aedes taeniorhynchus (Wied.) (MIR 0.34-0.36/1,000). WNV was also identified in and isolated from the pool of thoraxes and abdomens of Culex quinquefasciatus Say (4.17/1,000) and identified in one pool of thoraxes and abdomens of Culex habilitator Dyar and Knab (13.39/1,000). Accumulated evidence since 2002 suggests that WNV has not become endemic in Puerto Rico.

Variability of TSNA in U.S. Tobacco and Moist Smokeless Tobacco Products.

Tobacco-specific nitrosamines (TSNAs) have been of concern to the public health community for decades and their reduction through agricultural practices, plant breeding, and tobacco processing has also been a decades-long industry effort. Despite those efforts, TSNAs, though lower, continue to be constituents of concern in tobacco products. This paper examines the TSNA levels of dark air-cured, dark fire-cured, and burley tobaccos purchased in the United States by U.S. Smokeless Tobacco Company LLC (USSTC) and of nine finished USSTC moist smokeless tobacco products. TSNA values of the incoming purchased tobaccos and the finished products showed considerable variability. For the incoming tobaccos, the coefficient of variation was generally more than 100 % for each tobacco type and for each of the measured TSNAs. The relative TSNA variability of the finished tobacco products was also considerable, averaging approximately 25 %. It was also found that the measured values for the finished products averaged well above the proposed FDA NNN proposed product standard of 1.0 µg/g dry weight. Because of the large variability in NNN values, products would have to average well below FDA's proposed product standard to be consistently compliant.

Disorder in Al-li-cu and Al-mn-si icosahedral alloys.

Faceted dendrites of icosahedral AL(6)Li(3)Cu have been studied by high-resolution x-ray scattering. The samples display long-range icosahedral symmetry both in their diffraction patterns and in their macroscopic morphology. Despite the appearance of well-defined facets, the samples have a high degree of atomic disorder. The Bragg peaks have symmetry-dependent shapes and widths that scale linearly with G perpendicular (phason momentum). The peak widths are surprisingly similar to those found in icosahedral Al-Mn-Si alloys in both their absolute magnitude and their dependence on G perpendicular. The origin of these features in models for the icosahedral phase is discussed.

Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei.

The paradigm of antigenic variation in parasites is the variant surface glycoprotein (VSG) of African trypanosomes. Only one VSG is expressed at any time, except for short periods during switching. The reasons for this pattern of expression and the consequences of expressing more than one VSG are unknown. Trypanosoma brucei was genetically manipulated to generate cell lines that expressed two VSGs simultaneously. These VSGs were produced in equal amounts and were homogeneously distributed on the trypanosome surface. The double-expressor cells had similar population doubling times and were as infective as wild-type cells. Thus, the simultaneous expression of two VSGs is not intrinsically harmful.

C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with cyclosporin A.

Immunosuppressive treatments are available to suppress acute cardiac rejection; however, no viable treatment exists for long-term cardiac graft failure. Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay of the current therapeutic for cardiac transplantation, leads to significant associated pathologies such as nephrotoxicity and increased risk of cardiac disease. For the last ten years alternatives to calcineurin inhibitors, or adjuvant therapies designed to complement their activities, have been explored. In tandem with this development, there has been considerable interest in Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic rejection associated with cardiac transplantation. The objectives of this study were to first determine if oral delivery of the extract could reduce acute rejection in a rat heterotopic heart model of transplantation. The second objective was to determine, in vitro, if a sterile, aqueous extract of C. sinensis could decrease CD8+ T cell activity. The third objective was to determine if oral delivery of the extract could ablate allograft vasculopathy in a mouse abdominal aortic transplant model. We found that oral delivery of the extract demonstrated a reduction in acute rejection when used in conjunction with a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed lymphocyte reaction, that the extract was able to significantly reduce CD8+ T cell activity. Finally, we demonstrate that oral delivery of the extract, used with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates allograft vasculopathy.

Immune activation by a sterile aqueous extract of Cordyceps sinensis: mechanism of action.

Cordyceps sinensis is a fungus that has been used for over 2,000 years in China as a treatment for a variety of conditions including infectious diseases. The available evidence suggests a hypothesis that any efficacy of C. sinensis as an anti-infective therapeutic would be related to a role as an activator of innate immune responses. The objectives of this study were first to investigate the ability of C. sinensis to activate pro-inflammatory responses in macrophages in vitro and induce protective responses against intracellular pathogens in vivo, and second to characterize a method of action. We found that C. sinensis activates murine macrophages to produce a variety of pro-inflammatory cytokines. IFN-gamma synergizes with C. sinensis to amplify this response. Bacterial endotoxin contamination was ruled out as a potential artefact. The evidence presented in this study supports a hypothesis that C. sinensis activates macrophages by engaging Toll-like receptors and inducing mitogen-activated protein kinase (MAPK) pathways characteristic of inflammatory stimuli.

Evidence flowers: An innovative, visual method of presenting "best evidence" summaries to health professional and lay audiences.

BACKGROUND & AIMS: Barriers to dissemination and engagement with evidence pose a threat to implementing evidence-based medicine. Understanding, retention, and recall can be enhanced by visual presentation of information. The aim of this exploratory research was to develop and evaluate the accessibility and acceptability of visual summaries for presenting evidence syntheses with multiple exposures or outcomes to professional and lay audiences. METHODS: "Evidence flowers" were developed as a visual method of presenting data from 4 case scenarios: 2 complex evidence syntheses with multiple outcomes, Cochrane reviews, and clinical guidelines. Petals of evidence flowers were coloured according to the GRADE evidence rating system to display key findings and recommendations from the evidence summaries. Application of evidence flowers was observed during stakeholder workshops. Evaluation and feedback were conducted via questionnaires and informal interviews. RESULTS: Feedback from stakeholders on the evidence flowers collected from workshops, questionnaires, and interviews was encouraging and helpful for refining the design of the flowers. Comments were made on the content and design of the flowers, as well as the usability and potential for displaying different types of evidence. CONCLUSIONS: Evidence flowers are a novel and visually stimulating method for presenting research evidence from evidence syntheses with multiple exposures or outcomes, Cochrane reviews, and clinical guidelines. To promote access and engagement with research evidence, evidence flowers may be used in conjunction with other evidence synthesis products, such as (lay) summaries, evidence inventories, rapid reviews, and clinical guidelines. Additional research on potential adaptations and applications of the evidence flowers may further bridge the gap between research evidence and clinical practice.

Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1.

Trypanosoma brucei has telomeres composed of 15 kb tracts of TTAGGG repeats that end in 3' overhangs and form t-loops. This structure is also present in mammalian cells and is thought to reflect the presence of telomere-binding proteins. The human TTAGGG repeat-binding factor TRF1 binds to telomeres and regulates their length. We attempted to interfere with the normal function of trypanosome telomeres by expressing human TRF1 in T. brucei. TRF1 localized to telomeres in cultured procyclic (midgut-stage) trypanosomes with great fidelity, but not in bloodstream-stage trypanosomes. Procyclic trypanosomes expressing high levels of TRF1 for extended periods of time exhibited shortening and increased size heterogeneity of their telomeres and the cell cycle was arrested in G1-S. These effects were not detected in cells expressing a TRF1 mutant incapable of binding to TTAGGG repeats. We argue that TRF1 displaces putative endogenous trypanosome telomere-binding proteins, not yet identified, and affects telomeres in ways that reflect its role as a negative regulator of telomere length in human cells.

Differential effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptor antagonists applied to the basal forebrain on cortical acetylcholine release and electroencephalogram desynchronization.

It is known that glutamatergic tracts activated from the pedunculopontine tegmentum represent a major input to the nucleus basalis magnocellularis. To establish the role of different ionotropic glutamate receptors in synaptic transmission in the basal forebrain, the pedunculopontine tegmentum was stimulated in urethane-anesthetized rats and the resulting increases in cortical acetylcholine release and desynchronization of the electroencephalogram were monitored. R(-)-3-(2-carboxypiperazine-4-yl)-propyl-I-phosphonic acid (CPP), an antagonist at N-methyl-D-aspartate-type glutamate receptors, and 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), an antagonist at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, were delivered through a microdialysis probe placed in the basal forebrain. The N-methyl-D-aspartate antagonist preferentially inhibited cortical acetylcholine release, while the AMPA antagonist was more powerful in reducing desynchronization. A combination of both N-methyl-D-aspartate and AMPA antagonists abolished the increase in cortical acetylcholine release without reducing desynchronization. The dissociation between increased cortical acetylcholine release and electroencephalogram desynchronization suggests that the activity of corticopetal basal forebrain cholinergic neurons is neither necessary nor sufficient to produce electroencephalogram desynchronization. Rather, the nucleus basalis can probably affect the electroencephalogram by its projections to the thalamus. The reversal of the inhibitory effect of DNQX on the electroencephalogram by CPP may be due to the blockade of N-methyl-D-aspartate receptors on the GABAergic projection from the basal forebrain to the thalamus.

Distress and performance appraisal satisfaction.

120 quality assurance engineers indicated how frequently job stressors, causing distress related to role ambiguity, role conflict, role overload, and career development, affected them at work. They also indicated their satisfaction with their most recent performance appraisal. Satisfaction with performance appraisal was significantly negatively correlated with each stressor.

Effects of race on interrater reliability of peer ratings.

The effect of race on interrater reliability of peer ratings was investigated using data collected on 1,219 U.S. Army ROTC cadets at summer camp. White raters rating white ratees had a higher interrater reliability than black raters rating black ratees. Implications of this study are discussed.

Alcohol abuse and performance appraisal ratings.

274 adult volunteers completed a questionnaire concerning how different behaviors and emotions, which may be attributed to alcohol abuse, would affect their performance appraisal ratings of an individual who exhibited those behaviors or emotions. The appearance of behaviors and emotions that might signify alcohol abuse resulted in lower ratings. There was no difference between supervising and non-supervising raters or between male and female raters. Problems in permitting the symptoms to affect performance ratings are discussed.

Mechanics of particulate composites with glassy polymer binders in compression.

Whether used as structural components in design or matrix materials for composites, the mechanical properties of polymers are increasingly important. The compressive response of extruded polymethyl methacrylate (PMMA) rod with aligned polymer chains and Al-Ni-PMMA particulate composites are investigated across a range of strain rates and temperatures. The particulate composites were prepared using an injection-moulding technique resulting in highly anisotropic microstructures. The mechanics of these materials are discussed in the light of theories of deformation for glassy polymers. The experimental data from this study are compared with PMMA results from the literature as well as epoxy-based composites with identical particulates. The PMMA exhibited the expected strain rate and temperature dependence and brittle failure was observed at the highest strain rates and lowest temperatures. The Al-Ni-PMMA composites were found to have similar stress-strain response to the PMMA with reduced strain softening after yield. Increasing volume fraction of particulates in the composite resulted in decreased strength.

A phylogenetic analysis using full-length viral genomes of South American dengue serotype 3 in consecutive Venezuelan outbreaks reveals a novel NS5 mutation.

Dengue virus currently causes 50-100 million infections annually. Comprehensive knowledge about the evolution of Dengue in response to selection pressure is currently unavailable, but would greatly enhance vaccine design efforts. In the current study, we sequenced 187 new dengue virus serotype 3 (DENV-3) genotype III whole genomes isolated from Asia and the Americas. We analyzed them together with previously-sequenced isolates to gain a more detailed understanding of the evolutionary adaptations existing in this prevalent American serotype. In order to analyze the phylogenetic dynamics of DENV-3 during outbreak periods; we incorporated datasets of 48 and 11 sequences spanning two major outbreaks in Venezuela during 2001 and 2007-2008, respectively. Our phylogenetic analysis of newly sequenced viruses shows that subsets of genomes cluster primarily by geographic location, and secondarily by time of virus isolation. DENV-3 genotype III sequences from Asia are significantly divergent from those from the Americas due to their geographical separation and subsequent speciation. We measured amino acid variation for the E protein by calculating the Shannon entropy at each position between Asian and American genomes. We found a cluster of seven amino acid substitutions having high variability within E protein domain III, which has previously been implicated in serotype-specific neutralization escape mutants. No novel mutations were found in the E protein of sequences isolated during either Venezuelan outbreak. Shannon entropy analysis of the NS5 polymerase mature protein revealed that a G374E mutation, in a region that contributes to interferon resistance in other flaviviruses by interfering with JAK-STAT signaling was present in both the Asian and American sequences from the 2007-2008 Venezuelan outbreak, but was absent in the sequences from the 2001 Venezuelan outbreak. In addition to E, several NS5 amino acid changes were unique to the 2007-2008 epidemic in Venezuela and may give additional insight into the adaptive response of DENV-3 at the population level.