Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee

SummaryObjectiveThe aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-β1 (GEC-TGF-β1) compared to placebo.DesignA multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-β1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment.ResultsIKDC showed significant improvement in the GEC-TGF-β1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-β1 group compared to placebo at weeks 12 (LSMD: −13.8; P = 0.0162), 52 (LSMD: −13.1; P = 0.0332), and overall (LSMD: −10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-β1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed.ConclusionsGEC-TGF-β1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics.Trial Number: ClinicalTrials.gov (NCT01221441) – “Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee”

Age-Related Changes in the Behaviour of Domestic Horses as Reported by Owners

The broad traits of boldness and independence in domestic horses can affect their usefulness and, indirectly, their welfare. The objective of the current study was to explore associations between attributes that reflect equine boldness and independence with both the age of horses and the age at which they were started under saddle, as well as other variables including breed, colour and primary equestrian discipline. All data were sourced from responses (n = 1940) to the 97-question online Equine Behaviour Assessment and Research Questionnaire (E-BARQ). Twenty E-BARQ items from the dataset were selected to reflect boldness and independence and were tested for univariate significance at p < 0.2. Multivariable modelling of the effect of age on remaining traits was assessed by an ordinal logistic regression, using a cumulative log odds model. This revealed that older horses were bolder (p = 0.012). However, horses started under saddle at an older age were less bold and less independent (p = 0.040 and p = 0.010, respectively). Australian Stock Horses were bolder and more independent (p = 0.014 and p = 0.007, respectively) than crossbreed horses. Horses used for breeding conformation (p = 0.039), working equitation (p = 0.045), eventing (p = 0.044) and traditional working horses (p = 0.034) were bolder than those used for other disciplines. Dressage (p = 0.039) and therapy (p = 0.040) horses were less bold than horses used for other disciplines. Stallions were bolder (p = −0.034) than geldings. Brown (p = 0.049) and chestnut (p = 0.027) horses were less bold than bay horses. Compared to crossbreed horses, Thoroughbreds (p = 0.000) and companion horses (p = 0.017) were less bold whilst heavy horses (p = 0.029) and ponies (p = 0.044) were bolder. Compared to pleasure horses, mounted games horses (p = 0.033) were less independent whereas working equitation horses (p = 0.020) were more independent. Riders with more than eight years’ experience reported more independence in their horses (p = 0.015) than those who had ridden their whole lives. The study findings suggest that boldness and independence are separate traits and only boldness was associated with the age of the horse. Factors that relate to desirable boldness and independence are important in ridden horses because they can affect rider safety. Results from this study should improve horse–rider matching and thereby potentially enhance horse welfare

Associations between Owners’ Reports of Unwanted Ridden Behaviour and In-Hand Behaviour in Horses

An evidence-based understanding of dangerous or unwelcome behaviour in horses would greatly benefit both horses and humans who interact with them. Using owner-reported data from the Equine Behaviour Assessment and Research Questionnaire (E-BARQ), the current study investigated in-hand behaviours associated with dangerous or unwelcome ridden behaviours, notably bolting, rearing and bucking. Respondents (n = 1584) to the ridden horse section of the E-BARQ answered 42 demographic questions, followed by 268 behavioural items. Parallel analysis was conducted to group individual behaviours into rotated components to create independent and dependent indices. Multivariable general linear modelling and ordinal logistic regression were used to identify behaviours associated with bolting, rearing and bucking. Results revealed that safety-from-bolt increased as social confidence with horses (Odds ratio (OR) = 1.06; 95% confidence interval (cf = 1.02–1.09) and other animals (OR = 1.08; cf = 1.03–1.12), compliance in-hand (OR = 1.10; cf = 1.06–1.16) and tolerance of restraint (OR = 1.05; cf = 1.0–1.11) increased; and decreased as loading problems (OR = 0.95; cf = 0.92–0.99) increased. Safety-from-rear increased as tolerance of restraint (OR = 1.07; cf = 1.02–1.12) and social confidence with other animals (OR = 1.05; cf = 1.01–1.09) increased; and decreased as loading problems (OR = 0.94; cf = 0.91–0.98) increased. Safety-from-buck increased as social confidence with horses (b-value = 0.011, p < 0.001) and other animals (b-value = 0.010, p = 0.002), compliance in-hand (b-value = 0.015, p < 0.001), tolerance of restraint (b-value = 0.009, p = 0.027) and tolerance of haltering/bridling (b-value = 0.016, p = 0.010) increased, and it decreased as loading problems increased (b-value = −0.011, p < 0.001). By revealing, for the first time, that specific behaviours on the ground are associated with particular responses in the same horses when ridden, this study advances equitation science considerably. Identification of risk factors for dangerous behaviour while under saddle can improve safety for horses and riders and highlights the importance of effective and humane in-hand training