Development of a core outcome set for therapeutic clinical trials enrolling dogs with atopic dermatitis (COSCAD'18).

BACKGROUND: For decades, the efficacy of interventions in clinical trials enrolling dogs with atopic dermatitis (AD) relied on heterogeneous evaluations of skin lesions and pruritus using unvalidated tools. Although some instruments for clinical signs were validated later, there was little impact on standardizing outcome measures resulting in difficulties in comparing treatment efficacy between trials and impeding meta-analyses. RESULTS: Participants in the Outcome Measures subcommittee of the International Committee of Allergic Diseases of Animals (ICADA) collaborated for two years to develop a core outcome set (COS) for canine AD, the COSCAD. This project involved several steps, constantly-re-assessed during online exchanges, to define the scope of this COS, to identify the relevant stakeholders, the domains to be evaluated, the instruments available for measuring agreed-upon domains and how to express outcome measures. This COSCAD'18 was designed principally for therapeutic-but not preventive or proactive-clinical trials enrolling dogs with chronic, nonseasonal (perennial), moderate-to-severe AD. Selected domains were skin lesions, pruritus manifestations and perception of treatment efficacy. Instruments to evaluate these domains were the CADESI4 or CADLI, the 10-point pruritus visual analog scale (PVAS10) and the Owner Global Assessment of Treatment Efficacy (OGATE), respectively. The COSCAD'18 has three outcome measures: the percentages of dogs with veterinarian-assessed skin lesions or owner-rated pruritus manifestation scores in the range of normal dogs or those with mild AD; the third is a good-to-excellent global assessment by the pet owners of their perception of treatment efficacy. Importantly, this COSCAD'18 is not meant to represent the sole-or primary-outcome measures evaluated in a trial; authors are always free to add any others, which they deem will best assess the efficacy of tested interventions. Benchmarks to define a threshold for treatment success were not set, as what constitutes a clinically-relevant therapeutic efficacy is expected to vary greatly depending interventions. CONCLUSIONS: This COSCAD'18 should help veterinarians and owners compare the benefits of treatments in future trials. This COS should also facilitate the combination of trial results in future systematic reviews, thereby producing more reliable summary estimates of treatment effects and enhancing evidence-based veterinary dermatology.

Percutaneous prick test irritant threshold concentrations for eight allergens in healthy nonsedated dogs in the USA.

BACKGROUND: Percutaneous testing (PT) is preferred to intradermal testing in humans for the in vivo identification of allergen hypersensitivity, but the methodology has not been well described for use in dogs with atopic dermatitis. HYPOTHESIS/OBJECTIVES: To identify the irritant threshold concentrations (ITC) of eight aeroallergens using a commercial prick test device in normal dogs. ANIMALS: Twenty healthy, privately owned dogs. METHODS: Percutaneous testing was performed using the GREER® Pick® System (Stallergenes Greer; Lenoir, NC, USA). Five dilutions of glycerinated extracts of Bromis inermis, Sorghum halepense, Chenopodium album, Ambrosia psilostachya, Salix nigra and Acer negundo, as well as four dilutions of Dermatophagoides farinae and D. pteronyssinus were included. Glycerinated histamine (6 mg/ml) and glycerin/Coca's solution were used for the positive and negative controls, respectively. Orthogonal wheal diameters were measured for each test site every 5 min for 25 min. Reactions were considered significant when the average wheal diameter was equal to or greater than the mean of the positive and negative controls. RESULTS: Significant reactions were noted in five of 20 (25%) of dogs. The ITC (≤10% of dogs reacting) were 1:20 w/v for B. inermis and S. nigra, 1:400 w/v for D. farinae and 1:200 w/v for D. pteronyssinus. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that the pollen allergens evaluated in this study can be used for PT at their undiluted concentration (1:20 w/v) with a reasonable assurance of few false positive reactions in dogs. Dust mites require dilution for testing at the ITC.

Effectiveness of regionally-specific immunotherapy for the management of canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis is a common pruritic skin disease often treated with allergen immunotherapy (AIT). AIT in dogs traditionally begins with attempting to identify clinically relevant environmental allergens. Current allergen testing methodologies and immunotherapy techniques in dogs are not standardized. Immunotherapy with a mixture of allergenic extracts selected based on regional aerobiology rather than intradermal tests or serum IgE assays has been described. The objective of this study was to evaluate the effectiveness of regionally-specific immunotherapy in dogs with atopic dermatitis. The medical records of a veterinary dermatology referral clinic were searched for dogs with atopic dermatitis that began regionally-specific subcutaneous immunotherapy from June, 2010 to May, 2013. An overall assessment of treatment effectiveness (excellent, good, fair, or poor) was assigned based upon changes in pruritus severity, lesion severity, and the reduction in concurrent medication(s) during a follow-up period of at least 270 days. Baseline characteristics that might predict treatment success were analyzed with the Spearman's correlation and the Kruskal-Wallis tests. RESULTS: Of the 286 dogs that began regionally-specific immunotherapy (RESPIT) during a 3 year period, 103 met the inclusion criteria. The overall response to RESPIT was classified as excellent in 19%, good in 38%, fair in 25%, and poor in 18% of dogs. The response classification correlated significantly with a reduction in pruritus severity (r = 0.72, p < 0.001) and lesion severity (r = 0.54, p < 0.001), but not with the dogs' baseline characteristics. Adverse reactions were reported in 7/286 (2.4%) of treated dogs. CONCLUSIONS: Under the conditions of this study, RESPIT was safe and effective for the treatment of atopic dermatitis in dogs.

Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA.

BACKGROUND: Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. METHODS: Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT(®) , VARL Liquid Gold, ALLERCEPT(®) and Greer(®) Aller-g-complete(®) ). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. RESULTS: The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations.

Development and validation of the Canine Atopic Dermatitis Lesion Index, a scale for the rapid scoring of lesion severity in canine atopic dermatitis.

BACKGROUND: The third iteration of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) is the only tool rigorously validated for canine atopic dermatitis (CAD) lesion scoring. The CADESI-03 requires 248 evaluations, limiting its widespread use. HYPOTHESIS/OBJECTIVES: The goal of the study was to develop and validate a practical method of grading CAD lesions that requires scoring only the frequently affected body regions. ANIMALS: Fifty-seven privately owned atopic dogs were used in the study. METHODS: The Canine Atopic Dermatitis Lesion Index (CADLI) was evaluated in an open, multicentre reliability study. Validity was assessed with expert opinion (content validity) and comparison of CADLI with existing disease severity measures (construct and criterion validity). Reliability was evaluated by analysing repeated observations of each dog. Convenience was assessed in terms of the time required to complete the scale. RESULTS: The CADLI scores correlated with overall assessment scores (r = 0.60, P < 0.001, linear mixed model) and pruritus severity scores (r = 0.53, P < 0.001, linear mixed model), establishing construct validity. The CADLI was strongly correlated with CADESI-03 (r = 0.84, P < 0.001, linear mixed model), establishing criterion validity. The CADLI values obtained by two observers correlated very strongly (r = 0.91, P < 0.001), as did the repeat values for the same observer (r = 0.98, P < 0.001). The mean time to complete the CADLI was less than that required for CADESI-03 (1.9 and 12.6 min, respectively), a highly significant difference (P < 0.001). CONCLUSION AND CLINICAL IMPORTANCE: The CADLI was found to be an effective measure of CAD lesion severity, strongly correlating with CADESI-03. The convenience of CADLI makes it suitable for use in both clinical research and practice.

A case-control study of the risk factors for canine juvenile-onset generalized demodicosis in the USA.

Canine juvenile-onset generalized demodicosis (JOGD) is a common skin disorder suspected to be associated with multiple risk factors, including breed predispositions. These risk factors have not been well documented in a large population. A retrospective case-control study was conducted by searching the electronic medical records of 1,189,906 dogs examined at 600 hospitals during 2006 in order to assess the risk factors associated with JOGD in the USA. Multivariate analyses were conducted using logistic regression to estimate the relative risk with the odds ratio for variables hypothesized to influence the risk for canine demodicosis. Breeds (odds ratio) found to have the greatest association with a diagnosis of JOGD were American Staffordshire terrier (35.6), Staffordshire bull terrier (17.1) and Chinese shar-pei (7.2). Nonbreed risk factors (odds ratio) significantly associated with a diagnosis of JOGD were the diagnosis of pyoderma (5.5), coccidiosis (2.7) or hookworms (1.5), short coat (1.9) and nonenrollment in a preventative care wellness plan (1.5). Documenting these risk factors may help veterinarians to prioritize differential diagnoses and will aid in the design of prospective studies to elucidate the pathogenesis of demodicosis in dogs.

Repeatability and reproducibility of numerical rating scales and visual analogue scales for canine pruritus severity scoring.

Although they are used frequently in veterinary dermatology, the reliability of canine pruritus severity scales has not been reported. The objective of this study was to evaluate the reliability of pruritus severity numerical rating scales (NRS) and pruritus severity visual analogue scales (VAS). Videos of 16 dogs were evaluated for pruritus severity by 24 observers utilizing three NRS and three VAS. Intraobserver repeatability and interobserver reproducibility were evaluated with Cohen's kappa and Kendall's rank correlation statistics, respectively. The repeatability of pruritus severity NRS was fair, with mean Cohen's weighted kappa (kappa(w)) values ranging from 0.49 to 0.60. The mean Kendall's rank correlation coefficient (t) for the three VAS ranged from 0.62 to 0.73. The reproducibility of mid-range pruritus severity ranks was poor with both scale types. Scales describing overall pruritus severity were found to be reliable most consistently. Neither NRS nor VAS displayed the degree of reliability desired in a health measurement scale. Interpretation of research results evaluating canine pruritus severity with NRS and VAS scales should account for suboptimal reliability.

Frequency of appropriate and inappropriate presentation and analysis methods of ordered categorical data in the veterinary dermatology literature from January 2003 to June 2006.

Clinical outcomes that are difficult to measure directly are often graded with ordinal scales in the veterinary dermatology literature to approximate objective evaluation. Ordered categorical scales require statistical presentation and analysis methods consistent with the structure of the data. The objective of this study was to determine the frequency of inappropriate presentation and analysis methods of ordered categorical data in the recent veterinary dermatology literature. A total of 62 articles published between 1 January 2003 and 30 June 2006 in 16 journals reported categorical scales and were included in the study. The presentation and analysis methods of ordered categorical data were classified as appropriate or inappropriate based on published recommendations. Forty articles (64.5%) utilized a median of four ordinal scales (range 1-13). Inappropriate presentation methods of ordered categorical data were identified in 23 of 40 articles (57.5%). These included reporting inappropriate summary statistics (n = 17) and summation of ad hoc numerical rating scales (n = 15). Inappropriate analytical methods were used in nine of 40 articles (22.5%). These included inappropriate use of t-tests (n = 3) and analysis of variance (anova, n = 6). The frequency of inappropriate presentation and analysis methods of ordered categorical data in the veterinary dermatology literature is similar to that reported for several fields in the human medical literature. In order to reduce the likelihood of making unwarranted implications or conclusions regarding ordinal data, authors should follow established guidelines for methods of presentation and analysis of ordered categorical scales.

Efficacy of topical eprinomectin in the treatment of Chorioptes sp. infestation in alpacas and llamas.

Chorioptes sp. mite infestation is increasingly recognized as a cause of skin disease in New World camelids and there is a need for an effective treatment protocol to eliminate herd infestation. In this field trial, eprinomectin applied topically at the rate of 0.5 mg kg(-1) weekly for 10 weeks was found to be ineffective in a herd of 12 llamas and 16 alpacas.

Incorporating an audience response system into veterinary dermatology lectures: effect on student knowledge retention and satisfaction.

Veterinary educators are charged with delivering large amounts of information to adult students, who benefit from a more interactive learning environment than is often achieved through didactic lectures. Audience response systems (ARS) with wireless keypad technology facilitate interactive learning and have been used successfully in the education of health professionals. The objectives of this pilot study were to determine the effect of an ARS on the knowledge retention of veterinary dermatology students and to survey student attitudes concerning its use. A cohort-controlled trial was conducted to evaluate the potential benefits of ARS for short-term and long-term knowledge retention. Students also participated in four hours of student-directed case simulations using ARS technology. Students were surveyed regarding opinions on the use of the ARS. The mean short-term knowledge-retention test scores of groups A (ARS+) and B (ARS-) were 81% and 78%, respectively. The mean long-term knowledge-retention test scores of groups A and B were 54% and 55%, respectively. The differences between groups were not significant for either time period (p = 0.32, p = 0.77). Although benefits to short-term and long-term knowledge retention were not detected in this pilot study, all students responding to the survey perceived a benefit and supported the use of ARS in the clinical veterinary curriculum. ARS technology provides a tool for lecturers to create an interactive learning environment well suited for teaching veterinary dermatology.