Conduct,Oversight, and Ethical Considerations of Clinical Trials in Companion Animals with Cancer: Report of a Workshop on Best Practice Recommendations

Development of effective and safe treatments for companion animals with cancer requires the collaboration of numerous animal health professionals and the full engagement of animal owners. Establishing ‘Best Practice Recommendations’ for clinical trials in veterinary oncology represents an important step toward meeting the goal of rigorous clinical trial design and conduct that is required to establish valid evidence. Likewise, optimizing patient welfare and owner education and advocacy is crucial to meet the unique ethical obligations to both owners and animals enrolled in these clinical trials and to ensure trust in the team conducting the research. To date, ‘Best Practice Recommendations’ for clinical trial conduct have not been reported for veterinary oncology. This document summarizes the consensus of a workshop held in November, 2014 to identify relevant ethical principles and to ensure responsible conduct of clinical research in companion animals with cancer. It is intended as a working document that will be updated as advances in science and ethical considerations require. To the extent possible, existing guidelines for the conduct and oversight of clinical trials in humans have been adapted for veterinary trials to avoid duplicative effort and to facilitate integration of clinical trials such that translational research with benefits for both companion animals and humans are encouraged.     

Susceptibility of wild carrot (Daucus carota ssp. carota) to Sclerotinia sclerotiorum

Sclerotinia soft rot, caused by Sclerotinia sclerotiorum, is a severe disease of cultivated carrots (Daucus carota ssp. sativus) in storage. It is not known whether Sclerotinia soft rot also affects wild carrots (D. carota ssp. carota), which hybridise and exchange genes, among them resistance genes, with the cultivated carrot. We investigated the susceptibility of wild carrots to S. sclerotiorum isolates from cultivated carrot under controlled and outdoor conditions. Inoculated roots from both wild and cultivated plants produced sclerotia and soft rot in a growth chamber test. Two isolates differed significantly in the ability to produce lesions and sclerotia on roots of both wild carrots and cv. Bolero. Flowering stems of wild carrots produced dry, pale lesions after inoculation with the pathogen, and above-ground plant weight was significantly reduced 4 weeks after inoculation in a greenhouse test. Wild and cultivar rosette plants died earlier and fewer plants survived when inoculated with the pathogen under outdoor test conditions. Cultivar plants died earlier than wild plants, but survived as frequently. Plants inoculated in the crown died earlier and at a lower frequency than plants inoculated on leaves. Wild carrots may thus serve as a host of S. sclerotiorum and thus eventually benefit from any uptake of resistance genes, among them transgenes, via introgression from cultivated carrots.     

Effect of subchondral drilling on repair of partial-thickness cartilage defects of third carpal bones in horses

Arthrotomies of middle carpal joints were done on 13 horses, and a 1-cm partial thickness, round defect was made on the radial facet of both third carpal bones. In one joint, 1-mm diameter 1-cm deep holes were drilled within the defect, and one joint was used as a control. horses were assigned to 2 groups--group 1 (n = 6 horses), 5 drill holes; group 2 (n = 7 horses), 11 drill holes. At 1 and 3 weeks after surgery, differences between joints in synovial fluid total protein values, WBC counts, or results of mucin precipitate tests were not significant (P = 0.005). Physically and radiographically, horses were the same during the 12 initial weeks they were housed in stalls and the 9 weeks they were kept in paddocks. Twenty-one weeks after surgery, horses were euthanatized. Joints with drill holes had a significantly greater area (P less than 0.05) of healthy fibrocartilage new tissue: group 1-33 to 68% new tissue, compared with 0 to 23% new tissue in controls; and group 2-22 to 64% new tissue, compared with 0 to 37% new tissue in controls. Differences between healing of defects with drill holes in groups 1 and 2 were not significant. Thickness of new tissue over drill holes was 33 to 61% of thickness of cartilage adjacent to the defect, and thickness of tissue between drill holes was 11 to 43% (group 1) and 8 to 79% (group 2) of the thickness of cartilage adjacent to the defect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of a metallic foreign body in the cranial cervical region of a horse

Ingestion of foreign bodies is uncommon in horses when compared with indiscriminate grazers such as cattle. This case report describes the diagnosis and treatment of a cervical abscess in a Thoroughbred racehorse thought to be associated with ingestion of wire. Radiographic and ultrasonographic examination provided a diagnosis, and conservative treatment of the lesion with antimicrobials initially allowed the lesion to localise closer to the skin for safer surgical exploration. Intra-operative ultrasonographic imaging facilitated surgical access, removal of the foreign body, and drainage. While surgical treatment is usually necessary to resolve an abscess, initially conservative therapy may help to improve the prognosis by simplifying surgical access and reducing the risk of surgical complications.     

Modelling land use strategies to optimise crop production and protection of ecologically important weed species

There is a need to develop farming systems that enable both a satisfactory level of crop production and suitable environmental conditions for natural species. Wildlife‐friendly cropping techniques, such as a reduced amount of applied herbicide or a lower crop density, might be adopted in order to maintain populations of weed species of biological interest. An alternative might be to adopt an intensive cropping system in a part of the field and spare the other part as set‐aside or field margins, available for the natural development of plant species. The objective of this study was to present a method to compare two strategies for maintaining a desirable level of abundance of a given species of interest in agricultural areas, specifically (i) a strategy based on a wildlife‐friendly cropping system in a large cultivated area and (ii) a strategy based on a more intensive cropping system in a reduced area of cultivation, i.e. with land‐sparing. The principle is to calculate the ratio of crop production obtained with strategy (i) to the production obtained with strategy (ii) for a given target density of natural species. We show that the value of this ratio, and thus the relative performance of the two strategies, depends on the density of the weed species that can be maintained in an uncultivated ecological area. The method is applied in case studies of two plant species with contrasting ecology and conservation goals. The numerical results show that the strategy based on a wildlife‐friendly cropping system is more profitable in most situations.     

Progress in the development of tuberculosis vaccines for cattle and wildlife

Vaccination against bovine tuberculosis is likely to become an important disease control strategy in developing countries, which cannot afford a test and slaughter control programme, or in countries which have a wildlife reservoir of Mycobacterium bovis infection. In the past decade, considerable progress has been made in the development and evaluation of tuberculosis vaccines for cattle and for a range of wildlife maintenance hosts including possums, badgers, deer and African buffaloes. Experimental challenge systems have been established for the different target species and the resulting disease process has mimicked that seen in the field. In cattle, neonatal vaccination with BCG appeared to be more effective than vaccination of 6-month-old calves and in most situations no other vaccine has been shown to be better than BCG. However, prime-boost strategies involving combinations of BCG with a protein or DNA vaccine, to improve on BCG vaccination alone, have produced very encouraging results. Differential diagnostic tests have been developed using mycobacterial antigens that are only present in virulent M. bovis to differentiate between BCG-vaccinated and M. bovis-infected cattle. BCG vaccine has been shown to reduce the spread of tuberculous lesions in a range of wildlife species and a prototype oral bait delivery system has been developed. Prospects for the development of improved vaccines against bovine tuberculosis are promising and vaccination approaches could become very valuable in the control and eradication of bovine tuberculosis.     

Assessment of in vitro interferon-gamma responses from peripheral blood mononuclear cells of cattle infected with Mycoplasma mycoides ssp. mycoides small colony type

Contagious bovine pleuropneumonia (CBPP) is a lung disease caused by the bacterial pathogen Mycoplasma mycoides ssp. mycoides small colony type (MmmSC). It has been spreading due to a number of factors including poor vaccine efficacy and poor sensitivity of current diagnostic tests. The purpose of this study was to assess interferon gamma (IFN-gamma) release after stimulation of peripheral blood mononuclear cells (PBMC) from experimentally infected cattle. PBMC collected from 15 artificially infected animals were incubated with different concentrations of total MmmSC antigen. After 72h of incubation the IFN-gamma release was measured and found to be elevated in 11 animals. We did not observe a correlation between IFN-gamma release of animals with and without pathomorphological gross lesions. Therefore, our data do not confirm a role for CD4 T-lymphocytes in protection, since there is no correlation between IFN-g secretion (supposed to be mainly derived from CD4 T-cells) and disease severity. Additionally, we applied immunocytochemistry on affected lung tissue and detected no build up of T-lymphocytes (CD4 T-cells, CD8 T-cells) but a high presence of myeloid cells.     

Shedding of lymphoid leukosis virus in chickens following contact exposure and vaccination

Chickens contact-exposed to lymphoid leukosis virus at various ages up to 32 weeks responded with relatively high rates of infection as determined by the presence of neutralizing antibody. Virus shedding as determined by cloacal swab and albumen testing occurred in 7 of 8 groups of such chickens, but the incidence was 10% or less and sporadic. Vaccination of chickens immediately before exposure with a low pathogenicity virus of subgroup A at 8 weeks of age did not eliminate subsequent shedding.