231 research outputs found

    The changing global distribution and prevalence of canine transmissible venereal tumour.

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    BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer that is naturally transmitted between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT first arose several thousand years ago and has been reported in dog populations worldwide; however, its precise distribution patterns and prevalence remain unclear. RESULTS: We analysed historical literature and obtained CTVT prevalence information from 645 veterinarians and animal health workers in 109 countries in order to estimate CTVT's former and current global distribution and prevalence. This analysis confirmed that CTVT is endemic in at least 90 countries worldwide across all inhabited continents. CTVT is estimated to be present at a prevalence of one percent or more in dogs in at least 13 countries in South and Central America as well as in at least 11 countries in Africa and 8 countries in Asia. In the United States and Australia, CTVT was reported to be endemic only in remote indigenous communities. Comparison of current and historical reports of CTVT indicated that its prevalence has declined in Northern Europe, possibly due to changes in dog control laws during the nineteenth and twentieth centuries. Analysis of factors influencing CTVT prevalence showed that presence of free-roaming dogs was associated with increased CTVT prevalence, while dog spaying and neutering were associated with reduced CTVT prevalence. Our analysis indicated no gender bias for CTVT and we found no evidence that animals with CTVT frequently harbour concurrent infectious diseases. Vincristine was widely reported to be the most effective therapy for CTVT. CONCLUSIONS: Our results provide a survey of the current global distribution of CTVT, confirming that CTVT is endemic in at least 90 countries worldwide. Additionally, our analysis highlights factors that continue to modify CTVT's prevalence around the world and implicates free-roaming dogs as a reservoir for the disease. Our analysis also documents the disappearance of the disease from the United Kingdom during the twentieth century, which appears to have been an unintentional result of the introduction of dog control policies.This is the author's accepted manuscript. The final version of this article has been published by BioMed Central: http://www.biomedcentral.com/1746-6148/10/168

    Variability of indication criteria in knee and hip replacement: an observational study

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    <p>Abstract</p> <p>Background</p> <p>Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication.</p> <p>Methods</p> <p>The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated.</p> <p>The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ<sub>5-95</sub>), variation coefficient (CV<sub>5-95</sub>) and weighted variation coefficient (WCV<sub>5-95</sub>) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV<sub>5-95</sub>. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity.</p> <p>Results</p> <p>The variability expressed as WCV<sub>5-95 </sub>was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate.</p> <p>Conclusions</p> <p>A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates.</p

    Reducing gender disparities in post-total knee arthroplasty expectations through a decision aid

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    BACKGROUND: Gender disparities in total knee arthroplasty utilization may be due to differences in perceptions and expectations about total knee arthroplasty outcomes. This study evaluates the impact of a decision aid on perceptions about total knee arthroplasty and decision-making parameters among patients with knee osteoarthritis. METHODS: Patients with moderate to severe knee osteoarthritis viewed a video about knee osteoarthritis treatments options, including total knee arthroplasty, and received a personalized arthritis report. An adapted version of the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain and physical function expectations following total knee arthroplasty before/after the intervention. These scores were compared to an age- and gender-adjusted means for a cohort of patients who had undergone total knee arthroplasty. Decision readiness and conflict were also measured. RESULTS: At baseline, both men and women had poorer expectations about post-operative pain and physical outcomes compared with observed outcomes of the comparator group. Following the intervention, women’s mean age-adjusted expectations about post- total knee arthroplasty pain outcomes improved (Pre: 27.0; Post: 21.8 [p =0.08; 95% CI −0.7, 11.0]) and were closer to observed post-TKA outcomes; whereas men did not have a significant change in their pain expectations (Pre: 21.3; Post: 19.6 [p = 0.6; 95% CI −5.8, 9.4]). Women also demonstrated a significant improvement in decision readiness; whereas men did not. Both genders had less decision conflict after the intervention. CONCLUSIONS: Both women and men with osteoarthritis had poor estimates of total knee arthroplasty outcomes. Women responded to the intervention with more accurate total knee arthroplasty outcome expectations and greater decision readiness. Improving patient knowledge of total knee arthroplasty through a decision aid may improve medical decision-making and reduce gender disparities in total knee arthroplasty utilization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-015-0473-x) contains supplementary material, which is available to authorized users

    The Extended Cleavage Specificity of Human Thrombin

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    Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1′-Ser/Ala/Gly/Thr, P2′-not acidic and P3′-Arg. Our analysis also identifies an important role for a P3′-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3′-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200–400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1–30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times

    An Exploratory Study of Primary Care Physician Decision Making Regarding Total Joint Arthroplasty

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    BACKGROUND: For patients to experience the benefits of total joint arthroplasty (TJA), primary care physicians (PCPs) ought to know when to refer a patient for TJA and/or optimize nonsurgical treatment options for osteoarthritis (OA). OBJECTIVE: To evaluate the ability of physicians to make clinical treatment decisions. DESIGN AND PARTICIPANTS: A survey, using ten clinical vignettes, of PCPs in Indiana. MEASUREMENTS: A test score (range 0 to 10) was computed based on the number of correct answers consistent with published explicit appropriateness criteria for TJA. We also collected demographic characteristics and physicians’ perceived success rate of TJA in terms of pain relief and functional improvement. RESULTS: There were 149 PCPs (response rate = 61%) who participated. The mean test score was 6.5 ± 1.5. Only 17% correctly identified the published success rate of TJA (i.e., ≥90%). In multivariate analysis, the only physician-related variables associated with test score were ethnicity, board status, and perceived success rate of TJA. Physicians who were white (P = .001), board-certified (P = .04), and perceived a higher success rate of TJA (P = .004) had higher test scores. CONCLUSIONS: PCP knowledge with respect to guideline-concordant care for OA could be improved, specifically in deciding when to consider TJA versus optimizing nonsurgical options. Moreover, the perception of the success rate of TJA may influence a clinician’s decision making

    A comparison of genomic profiles of complex diseases under different models

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    Background: Various approaches are being used to predict individual risk to polygenic diseases from data provided by genome-wide association studies. As there are substantial differences between the diseases investigated, the data sets used and the way they are tested, it is difficult to assess which models are more suitable for this task. Results: We compared different approaches for seven complex diseases provided by the Wellcome Trust Case Control Consortium (WTCCC) under a within-study validation approach. Risk models were inferred using a variety of learning machines and assumptions about the underlying genetic model, including a haplotype-based approach with different haplotype lengths and different thresholds in association levels to choose loci as part of the predictive model. In accordance with previous work, our results generally showed low accuracy considering disease heritability and population prevalence. However, the boosting algorithm returned a predictive area under the ROC curve (AUC) of 0.8805 for Type 1 diabetes (T1D) and 0.8087 for rheumatoid arthritis, both clearly over the AUC obtained by other approaches and over 0.75, which is the minimum required for a disease to be successfully tested on a sample at risk, which means that boosting is a promising approach. Its good performance seems to be related to its robustness to redundant data, as in the case of genome-wide data sets due to linkage disequilibrium. Conclusions: In view of our results, the boosting approach may be suitable for modeling individual predisposition to Type 1 diabetes and rheumatoid arthritis based on genome-wide data and should be considered for more in-depth research.This work was supported by the Spanish Secretary of Research, Development and Innovation [TIN2010-20900-C04-1]; the Spanish Health Institute Carlos III [PI13/02714]and [PI13/01527] and the Andalusian Research Program under project P08-TIC-03717 with the help of the European Regional Development Fund (ERDF). The authors are very grateful to the reviewers, as they believe that their comments have helped to substantially improve the quality of the paper
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