Minimal clinically-important differences for the "Liverpool Osteoarthritis in Dogs" (LOAD) and the "Canine Orthopedic Index" (COI) in dogs with osteoarthritis.

ObjectiveOsteoarthritis is the most common joint disease in companion animals. Several client-report outcome measures (CROMs) have been developed and validated to monitor patients and their response to treatment. However, estimates for minimal clinically-important differences for these CROMs in the context of osteoarthritis have not been published.Patients and methodsData from the Clínica Veterinária de Cães (Portuguese Gendarmerie Canine Clinic) clinical records were extracted. Baseline and 30-day post-treatment follow-up data from 296 dogs treated for hip osteoarthritis were categorized based on an anchor question, and estimates of minimal clinically-important differences (MCIDs) using distribution-based and anchor-based methods were performed.ResultsFor the LOAD, the anchor-based methods provided a MCID estimate range of -2.5 to -9.1 and the distribution-based methods from 1.6 to 4.2. For the COI, the anchor-based methods provided a MCID estimate range of -4.5 to -16.6 and the distribution-based methods from 2.3 to 2.4. For the dimensions of COI, values varied from -0.5 to -4.9 with the anchor-based methods and from 0.6 to 2.7 with the distribution-based methods. Receiver operator characteristic curves provided areas under the curve >0.7 for the COI, indicating an acceptable cut-off point, and >0.8 for the LOAD, indicating an excellent cut-off point.ConclusionOur estimates of MCIDs for dogs with OA were consistent with previously proposed values of -4 for the LOAD and -14 for the COI in a post-surgical intervention context. ROC curve data suggest that LOAD may more reliably differentiate between anchor groups. We also presented estimates from COI of -4 for Stiffness, Function, and Gait and -3 for quality of life. These estimates can be used for research and patient monitoring

An exploration of the ability of tepoxalin to ameliorate the degradation of articular cartilage in a canine in vitro model

<p>Abstract</p> <p>Background</p> <p>To study the ability of tepoxalin, a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX) and its active metabolite to reduce the catabolic response of cartilage to cytokine stimulation in an <it>in vitro </it>model of canine osteoarthritis (OA).</p> <p>Grossly normal cartilage was collected post-mortem from seven dogs that had no evidence of joint disease. Cartilage explants were cultured in media containing the recombinant canine interleukin-1<it>β </it>(IL-1<it>β</it>) at 100 ng/ml and recombinant human oncostatin-M (OSM) at 50 ng/ml. The effects of tepoxalin and its metabolite were studied at three concentrations (1 × 10^-5, 1 × 10^-6and 1 × 10^-7M). Total glycosaminoglycan (GAG) and collagen (hydroxyproline) release from cartilage explants were used as outcome measures of proteoglycan and collagen depletion respectively. PGE₂and LTB₄assays were performed to study the effects of the drug on COX and LOX activity.</p> <p>Results</p> <p>Treatment with IL-1<it>β </it>and OSM significantly upregulated both collagen (p = 0.004) and proteoglycan (p = 0.001) release from the explants. Tepoxalin at 10^-5M and 10^-6M caused a decrease in collagen release from the explants (p = 0.047 and p = 0.075). Drug treatment showed no effect on GAG release. PGE₂concentration in culture media at day 7 was significantly increased by IL-1<it>β </it>and OSM and treatment with both tepoxalin and its metabolite showed a trend towards dose-dependent reduction of PGE₂production. LTB₄concentrations were too low to be quantified. Cytotoxicity assays suggested that neither tepoxalin nor its metabolite had a toxic effect on the cartilage chondrocytes at the concentrations and used in this study.</p> <p>Conclusion</p> <p>This study provides evidence that tepoxalin exerts inhibition of COX and can reduce <it>in vitro </it>collagen loss from canine cartilage explants at a concentration of 10^-5M. We can conclude that, in this model, tepoxalin can partially inhibit the development of cartilage degeneration when it is available locally to the tissue.</p

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: implications for reinfection

Background: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). Methods: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. Results: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75–12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01–1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29–2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84–3.64). Conclusion: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection

Analysis of normal and osteoarthritic canine cartilage mRNA expression by quantitative polymerase chain reaction

The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised that the expression of selected proteases, matrix molecules, and collagens believed to have a role in the pathogenesis of OA would be changed in naturally occurring canine OA cartilage when compared to normal articular cartilage. Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays were designed measuring the expression of selected matrix molecules (collagens and small leucine-rich proteoglycans), key mediators of the proteolytic degradation of articular cartilage (metalloproteinases, cathepsins), and their inhibitors (tissue inhibitors of matrix metalloproteinases). All data were normalised using a geometric mean of three housekeeping genes, and the results subjected to power calculations and corrections for multiple hypothesis testing. We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1, CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA. The expression of TIMP2 and TIMP4 was significantly reduced in canine OA cartilage. The patterns of gene expression change observed in naturally occurring canine OA were similar to those reported in naturally occurring human OA and experimental canine OA. We conclude that the expression profiles of matrix-associated molecules in end-stage mammalian OA may be comparable but that the precise aetiologies of OA affecting specific joints in different species are presently unknown

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (&#60;35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain

BackgroundThere is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups.ResultsCBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006).ConclusionsThese pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0413-x) contains supplementary material, which is available to authorized users

Dynamical Masses for Low-Mass Pre-Main Sequence Stars: A Preliminary Physical Orbit for HD 98800 B

We report on Keck Interferometer observations of the double-lined binary (B) component of the quadruple pre-main sequence (PMS) system HD 98800. With these interferometric observations combined with astrometric measurements made by the Hubble Space Telescope Fine Guidance Sensors (FGS), and published radial velocity observations we have estimated preliminary visual and physical orbits of the HD 98800 B subsystem. Our orbit model calls for an inclination of 66.8 $\pm$ 3.2 deg, and allows us to infer the masses and luminosities of the individual components. In particular we find component masses of 0.699 $\pm$ 0.064 and 0.582 $\pm$ 0.051 M_{\sun} for the Ba (primary) and Bb (secondary) components respectively. Modeling of the component SEDs finds temperatures and luminosities in agreement with previous studies, and coupled with the component mass estimates allows for comparison with PMS models in the low-mass regime with few empirical constraints. Solar abundance models seem to under-predict the inferred component temperatures and luminosities, while assuming slightly sub-solar abundances bring the models and observations into better agreement. The present preliminary orbit does not yet place significant constraints on existing pre-main sequence stellar models, but prospects for additional observations improving the orbit model and component parameters are very good.Comment: 20 pages, 6 figures, ApJ in press; tables 2 and 3 to be included in ApJ versio

An in vitro comparison of the neurotrophic and angiogenic activity of human and canine adipose-derived mesenchymal stem cells (MSCs): translating MSC-based therapies for spinal cord injury.

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and a comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, CD immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and βIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI, furthermore it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI