Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data.

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.

Economic evaluation of antimicrobial usage surveillance in livestock.

There is increased pressure by governments and industry to develop national surveillance programmes to evaluate antimicrobial usage (AMU) in animals. This article presents a methodological approach to cost-effectiveness analysis of such programmes. Seven objectives are proposed for AMU surveillance in animals: quantifying use, finding trends, detecting hotspots, identifying risk factors, encouraging research, evaluating the impact of policies and diseases, and demonstrating compliance with regulations. Achieving these objectives would assist in making decisions about potential interventions, help to generate trust, incentivise the reduction of AMU and decrease the risk of antimicrobial resistance. The cost-effectiveness of each objective can be found by dividing the cost of the programme by the performance indicators of the surveillance required to meet the objective concerned. The precision and accuracy of surveillance outputs are suggested here as useful performance indicators. Precision depends on the level of surveillance coverage (SC) and surveillance representativeness (SR). Accuracy is influenced by the quality of farm records and SR. The authors argue that there is an increase in marginal cost for each unit increase of SC, SR and data quality. This is caused by the increasing difficulty of recruiting farmers due to potential barriers such as staff capacity, capital availability, computing literacy and availability, and geographical differences, among other factors. A simulation model was conducted to test the approach, using the quantification of AMU as the primary objective, and to provide evidence of the application of the law of diminishing returns. Cost-effectiveness analysis can be used to support decisions on the level of coverage, representativeness and data quality required in such AMU programmes.

Les gouvernements tout comme le secteur de l'élevage exercent une pression croissante pour que des programmes nationaux de surveillance soient élaborés afin d'évaluer l'utilisation d'agents antimicrobiens (UAM) chez les animaux. Cet article présente une approche méthodologique permettant de réaliser l'analyse coût-efficacité de ces programmes. Sept objectifs sont proposés pour la surveillance de l'UAM chez les animaux : quantifier cette utilisation, relever les tendances, détecter les situations d'utilisation intensive, déceler les facteurs de risque, encourager la recherche, évaluer l'impact des politiques et des maladies et démontrer la conformité avec les réglementations. La réalisation de ces objectifs de surveillance permettra de prendre des décisions éclairées sur les interventions à mener, contribuera à mettre en place un climat de confiance, encouragera à réduire l'UAM et atténuera le risque d'apparition d'antibiorésistances. Le ratio coût-efficacité de chaque objectif peut être déterminé en divisant le coût du programme par les indicateurs de performance de la surveillance requise pour chacun des objectifs examinés. Les auteurs considèrent que la précision et l'exactitude des résultats de la surveillance sont des indicateurs de performance utiles à cet effet. La précision dépend du niveau de couverture de la surveillance (CS) et de sa représentativité (RS). L'exactitude est fonction de la qualité des registres d'élevage et de la RS. D'après les auteurs, chaque accroissement unitaire de la CS, de la RS et de la qualité des données donne lieu à une augmentation du coût marginal. Celle-ci s'explique par la difficulté croissante de recruter des éleveurs pour cette activité, en raison d'obstacles tels que le manque d'effectifs, la disponibilité de capitaux, le manque de compétences et d'équipements informatiques et les différences géographiques, entre autres facteurs potentiels. Un modèle de simulation a été mis en oeuvre pour tester cette approche à partir de l'objectif principal (la quantification de l'UAM), et pour apporter des éléments démontrant l'application de la loi des rendements décroissants dans ce domaine. L'analyse coût-efficacité peut être utilisée pour étayer les décisions concernant la couverture, la représentativité et la qualité des données requises pour les programmes de surveillance de l'UAM.

Los gobiernos y la industria vienen presionando cada vez más para la implantación de programas nacionales de vigilancia destinados a evaluar el uso de agentes antimicrobianos (UAM) en los animales. Los autores presentan una solución metodológica para analizar la relación costo-eficacia de tales programas. En primer lugar proponen un conjunto de siete objetivos que deben cumplirse al vigilar el UAM en los animales: cuantificar el uso, detectar tendencias, localizar áreas de "gran intensidad" de uso, determinar los factores de riesgo, alentar la investigación, evaluar la repercusión de las políticas y las enfermedades y comprobar la observancia de los reglamentos. El logro de estos objetivos ayudaría a decidir sobre posibles intervenciones y a generar confianza, supondría un incentivo para reducir el UAM y atenuaría el riesgo de que surgieran resistencias a estos productos. Para cada objetivo es posible determinar la relación costo-eficacia dividiendo el costo del programa por los indicadores de desempeño de la vigilancia requerida para cumplir el objetivo en cuestión. Los autores proponen utilizar la precisión y exactitud de los resultados de la vigilancia como útiles indicadores de desempeño. La precisión depende del nivel de cobertura y de representatividad de la vigilancia. En la exactitud, por su parte, influyen la calidad de los archivos de las explotaciones pecuarias y la representatividad de la vigilancia. Los autores postulan que cada aumento unitario de la cobertura y la representatividad de la vigilancia y de la calidad de los datos se acompaña de un aumento correspondiente del costo marginal. Ello se explica por la creciente dificultad que presenta la participación de ganaderos en el proceso, debida a su vez a posibles barreras en aspectos como la dotación de personal, el capital disponible, los conocimientos en informática y el acceso a ordenadores o las diferencias geográficas, entre otros factores. Para ensayar el método y probar que se aplica el principio de los rendimientos decrecientes, los autores emplearon un modelo de simulación, utilizando como principal objetivo la cuantificación del UAM. El análisis de la relación costo-eficacia puede ser utilizado como herramienta auxiliar para tomar decisiones sobre el nivel de cobertura, representatividad y calidad de los datos que se necesita en este tipo de programas de vigilancia del UAM.

Effects of external ambient temperature at loading, journey duration and flock characteristics on the dead-on-arrival rate in broiler chickens transported to slaughter in Great Britain.

Broiler mortality during transport and lairage, prior to slaughter, has negative welfare and economic implications. Knowledge of the factors affecting the dead-on-arrival (DOA) rate can help identify risk-mitigating strategies. The objectives of this study were to determine the DOA rate in broiler chickens transported to slaughter in Great Britain and associated risk factors. Requested data for all loads of broilers transported to slaughter by 5 large British commercial companies on 57 randomly-selected dates in 2019 were obtained and combined with weather data extracted from the Met Office MIDAS Open database. The DOA rate was described overall and per load using summary descriptive statistics. Mixed-effects Poisson regression was used to evaluate considered flock-, journey- and weather-related risk factors. Results were reported as incidence rate ratios (IRR) and 95% confidence intervals (CI). On the selected dates, 25,476 loads transported 146,219,189 broilers to slaughter. The overall mean DOA rate was 0.08%. The median DOA rate per load was 0.06% (interquartile range 0.03-0.09%; range 0.00-17.39%). Multiple risk factors were identified including loading temperature and catch method. At relative humidity ≤80%, the DOA rate was 16.89 (95% CI 15.25-18.70, P < 0.001) times higher for loads loaded in external ambient temperatures >30.0°C compared to those loaded in temperatures between 10.1°C and 15.0°C. When relative humidity was >80%, there was a 43% increase in DOA rate for loads loaded in temperatures below freezing compared to those loaded in temperatures between 10.1°C and 15.0°C (IRR 1.43, 95% CI 1.35-1.52, P < 0.001). The DOA rate was 32% higher for loads caught mechanically compared to those caught manually (IRR 1.32, 95% CI 1.23-1.42, P < 0.001). The overall DOA rate was lower than that previously reported in Great Britain and for other European countries. Most identified risk factors had a marginal effect, however, loading temperatures >30°C substantially increased DOA rate. Internal thermal environmental conditions were not evaluated. Avoidance of loading during periods of hot weather would improve the welfare of, and reduce economic losses in, broiler chickens.

Outcome of chronic inflammatory enteropathy in cats: 65 cases (2011-2021).

OBJECTIVES: Feline chronic inflammatory enteropathy is an idiopathic disease with limited information on variables that might affect treatment outcome and survival. The aim of this study was to determine if clinicopathological variables were associated with death due to gastrointestinal disease in cats with chronic inflammatory enteropathy. MATERIALS AND METHODS: Three medical records databases were retrospectively searched for cats diagnosed with chronic inflammatory enteropathy at the Royal Veterinary College between June 2008 and November 2021. Intestinal biopsy specimens of eligible cases were re-reviewed by one board-certified veterinary pathologist. Outcome information was obtained by contact with the referring veterinary surgeon. Two univariable binary logistic regression models and a Fisher's exact test were performed to assess the association between the outcome of death due to gastrointestinal disease or its short-term survival (≤ versus >1 year) with clinicopathological variables and the attainment of clinical remission. RESULTS: Sixty-five cats diagnosed with chronic inflammatory enteropathy between September 2011 and August 2021 were included in the study with follow-up information available for 54 cats (83%). Of these 54 cats, 20 (37%) were euthanised due to gastrointestinal disease (median 129.5 days; range 8 to 2970 days). Twenty-five (46%) cats were alive and in clinical remission (median 916 days; range 78 to 2113 days) with 16 (64%) diagnosed with food-responsive enteropathy. Attaining clinical remission reduced the likelihood of subsequent death due to gastrointestinal disease. CLINICAL SIGNIFICANCE: Measured physical and laboratory variables at the time of histopathological diagnosis of chronic inflammatory enteropathy were not predictors of death. Alternative diagnostic measures are required to definitively investigate outcome and survival in cats with chronic inflammatory enteropathy.

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in ß-oxidation of fatty acids and an increased dependence upon glycolysis. OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. METHODS: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. RESULTS: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. CONCLUSIONS: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced ß-oxidation. This proposed explanation warrants further research.

Spatial links between subchondral bone architectural features and cartilage degeneration in osteoarthritic joints.

Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression.

[Levels of human milk oligosaccharides in breast milk of mothers delivering preterm infants of different gestational ages and their effects on early growth and development].

Objective: To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants. Methods: In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31+6 weeks) and moderate to late preterm (32-36+6 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), 3'-sialyllactose (3'SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2'-fucosyllactose (2'FL) concentration in colostrum and transitional milk greater than 200 µg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher's exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. Results: 79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ²=1.31,P>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 µg/mL, respectively (Kruskal-Wallis χ²=8.1234,P=0.044). When analyzed by the median weight gain of the infants (low vs high weight gain) at 4 months postpartum, 2'FL was significantly lower in the high weight gain group at 7 d (1 818.04 µg/mL vs 2 181.67 µg/mL, W=1 386,P=0.018), while LNT & LNnT were significantly higher (1 182.36 µg/mL vs 1 053.62 µg/mL, W=816,P=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 µg/mL vs 286.18 µg/mL, W=564,P=0.026). Conclusions: The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.

Associations between behaviour and health outcomes in conventional and slow-growing breeds of broiler chicken.

Broiler chickens are prone to a range of complex health and welfare issues. To support informed selection of welfare traits whilst minimising impact on production efficiency and to address a major gap in understanding, we systematically explored associations between health and behavioural indicators of broiler welfare. One conventional (CNV, n = 350) and two slow-growing broiler breeds (SGH and SGN, respectively n = 400) were reared from hatch in pens of 50 birds. Birds were assessed for health (gait, plumage cover and dirtiness, pododermatitis, hockburn, and leg deviations) at 2.2 kg liveweight according to the Royal Society for the Prevention of Cruelty to Animals Broiler Breed Welfare Assessment Protocol. Behaviour and resource-use of 10% of birds per pen, on days 29 (all breeds) and 43 (SGH and SGN), was (i) scan sampled every 60 min between three to six and between twelve to fifteen hours after photoperiod onset; and (ii) continuously sampled sequentially from focal birds for 3 min each in a random order, during 15 min observation periods at three and twelve hours after photoperiod onset. Binary logistic generalized linear models were used, to assess respective associations between pen prevalence of each health outcome and (i) pen mean percentage scans of behaviour, and (ii) pen mean frequency and duration per 3 min focal observation of behaviour. Better growth rate and feed conversion but poorer health outcomes (mortality, gait, pododermatitis, feather cover) were more prevalent in CNV. Strong associations between behaviour and several heath indicators revealed, (i) increases in side-lying inactive, sitting inactive, and use of the litter relative to other resources, as primary and general indicators of poorer health, and (ii) increases in standing inactive, perch use, walking, Comfort, High Energy and Exploratory behaviour as primary and general indicators of better health. Of these, changes in side-lying, standing inactive, walking, Comfort and High Energy behaviour were particularly sensitive to small differences in health outcomes important for breed acceptance in high-welfare schemes. Crucially these behavioural measures additionally represent motivational and affective aspects of welfare not captured by health measures and allow opportunity for earlier intervention. Thus, to provide a comprehensive assessment of broiler experience, behaviour should be incorporated into broiler welfare assessments.

Paroxysmal high-grade second-degree and persistent third-degree atrioventricular block in cats.

INTRODUCTION: Both paroxysmal high-grade second-degree and persistent third-degree atrioventricular block (AVB) are recognised in cats. Our aim was to document the presentation, echocardiographic data, comorbidities and outcome in affected cats from a single referral hospital, including those that underwent epicardial pacemaker implantation (EPI). ANIMALS, MATERIALS AND METHODS: This retrospective study included 64 cats diagnosed with persistent third-degree or paroxysmal high-grade AVB, for which detailed patient history was available. Non-parametric testing, Kaplan-Meier curves and Cox proportional hazard testing were performed. RESULTS: Atrioventricular block was persistent in 43 cats (67%) and paroxysmal in 21 (33%). Forty-seven cats (74%) were referred for cardiac complaints (e.g. collapse, arrhythmia, tachypnea), 6 (9%) had non-specific complaints and AVB was an incidental finding in 11 cats (17%). Median duration of clinical signs prior to presentation was 21 days (1-1138 days). Thirty-nine (63%) cats had echocardiographic abnormalities; 13 (20%) presented with congestive heart failure. Forty-five (70%) cats had one or more comorbidities. Fifteen cats underwent EPI with immediate resolution of signs in 12 cats. Following EPI, two and four cats experienced major and minor complications, respectively. Forty-seven cats died; median survival time was 799 days (all-cause mortality). Cardiac-related death occurred in 17 cats (36%); median survival in these cats was 132 days. Heart failure on presentation was the only independent risk factor for cardiac death (p=0.002). CONCLUSIONS: Outcome in cats with AVB was variable, although most had good medium- to long-term survival. Cardiac death occurred in a minority of cats. Pacemaker implantation was effective in relieving clinical signs.

Identification of production chain risk factors for slaughterhouse condemnation of broiler chickens'.

Slaughterhouse condemnation of broiler chickens results from identification of polymorphic pathological conditions during meat inspection from arrival and on the slaughter line. While conditions that result in condemnation are multifactorial, identification of factors that are common for a number of categories could be valuable for developing strategies to reduce total condemnation. This study aimed to identify those condemnation categories that were most common in batches of broiler chickens and to determine and compare associated risk factors. In the first step, retrospective meat inspection records for 55,918 broiler batches from one large broiler integrator for 2015-2017 were used for association rules analysis. Results identified a network of nine associated condemnation categories: whole carcass condemnation for ascites, abnormal colour, perihepatitis, cellulitis, hard breast, tumours and dead on arrival, and liver only and heart only most often associated with hepatitis and pericarditis, respectively. Secondly, a longitudinal study collected data on 109 explanatory variables from broiler parental flocks to slaughterhouse characteristics between January 2015 and December 2017. Condemnation outcome data were obtained from meat inspection records for 539 broiler batches participating in the study. Parental flock-, rearing farm-, shed- and transport-level risk factors were assessed for each outcome using mixed-effects multivariable Poisson regression including shed and farm as random effects. A Poisson regression tree method was used as the first step to identify variables most relevant for analysis and comparison across the outcomes. No single production factor was associated with all nine of the condemnation outcomes investigated in this study, although some were shared across multiple outcomes: age of parental flock at time of lay, flock-level Campylobacter spp. frequency, broiler chick weight at seven days of age, weight at slaughter, type of broiler removal (i.e. thinning, final depopulation), catcher team, number of birds per transport crate, slaughterhouse shift number, and type of slaughterhouse line. Broiler chickens removed during final depopulation were at greatest risk of condemnation. Condemnation rates for cellulitis and tumours were found to be higher in broilers inspected by night shift at the slaughterhouse. Discovery of an apparent protective effect of a higher number of broilers per transport crate was unexpected. These findings provide information for the broiler industry on production chain factors that might be amenable to targeted intervention to improve future efforts for control of condemnation.

Major Radiologic and Clinical Outcomes of Total Spine MRI Performed in the Emergency Department at a Major Academic Medical Center.

BACKGROUND AND PURPOSE: Total spine MRIs are requested by the emergency department when focused imaging can not be ordered on the basis of history or clinical findings. However, their efficacy is not known. We assessed the following: 1) major radiologic and clinical outcomes of total spine MR imaging performed by the emergency department, and 2) whether the presence of a high-risk clinical profile and/or neurologic findings impacts the clinical outcomes. MATERIALS AND METHODS: Total spine MRIs requested by the emergency department during a 28-month period were evaluated for major radiologic (cord compression, cauda equina compression, and other significant findings) and major clinical outcomes (hospital admission during the visit followed by an operation, radiation therapy, or intravenous antibiotics or steroids). Associations between a high-risk clinical profile (cancer, infection, coagulopathy) and/or the presence of neurologic findings and outcomes were assessed. RESULTS: After we excluded trauma or nondiagnostic studies, 321/2047 (15.7%) MRIs ordered during study period were total spine MR imaging; 117/321 (36.4%) had major radiologic and 60/321 (18.6%) had major clinical outcomes (34/60 in <24 hours); and 58/117(49.6%) with major radiologic outcome were treated compared with 2/205 (1.0%) without (OR = 99, P < .001). The presence of both a high-risk clinical profile and neurologic findings concurrently in a patient (142/321) increased the likelihood of major clinical outcomes during the same visit (OR = 3.1, P < .001) and in <24-hours (OR = 2.6, P = .01) compared with those with either a high-risk clinical profile or neurologic findings alone (179/321). CONCLUSIONS: Total spine MR imaging ordered by our emergency department has a high radiologic and significant clinical yield. When a high-risk clinical profile and neurologic findings are both present in a patient, they should be prioritized for emergent total spine MR imaging, given the increased likelihood of clinical impact.

Unilateral Nonvisualization of a Transverse Dural Sinus on Phase-Contrast MRV: Frequency and Differentiation from Sinus Thrombosis on Noncontrast MRI.

BACKGROUND AND PURPOSE: Unilateral decreased/nonvisualization of a transverse dural sinus on MRV poses a diagnostic dilemma when gadolinium administration is contraindicated. We determined the frequency of unilateral decreased/nonvisualization of the transverse dural sinus and the performance of pregadolinium MR imaging sequences in diagnosing transverse sinus thrombosis in the presence of unilateral decreased/nonvisualization on phase-contrast MRV. MATERIALS AND METHODS: We conducted a retrospective review of consecutive 3D phase-contrast MRV (VENC, 30 cm/s) and routine brain imaging (noncontrast sagittal T1, axial T2, FLAIR, DWI, GRE, and postgadolinium 3D-MPRAGE images) performed during a 3-year period for a total of 208 patients. Nonvisualization of a transverse dural sinus was defined as ≥50% nonvisualization of the transverse sinus caliber versus the contralateral side on MRV. Noncontrast imaging findings were considered abnormal when hyperintense signal was present on T2, FLAIR, T1, and DWI, and there were T2* blooming artifacts on GRE and DWI. Postgadolinium 3D-MPRAGE was used to confirm the diagnosis of transverse sinus thrombosis. RESULTS: Nonvisualization of a transverse dural sinus was observed in 72/208 (34.6%) patients on MRV; 56/72 (77.8%) were without transverse sinus thrombosis, and 16/72 (22.2%) patients had transverse dural sinus thrombosis. Nonvisualization of a transverse dural sinus was seen in 56/192 (29.2%) patients without transverse sinus thrombosis and 16/16 (100%) with transverse sinus thrombosis. Abnormal findings on DWI (transverse sinus hyperintense signal or T2* blooming artifact) are 93.8% sensitive and 100.0% specific for transverse sinus thrombosis. Other noncontrast MR imaging sequences ranged from 56.3%-68.8% sensitive and 91.1%-100.0% specific. CONCLUSIONS: Nonvisualization of a transverse dural sinus is a frequent phenomenon on phase-contrast MRV. DWI can be effectively used to exclude sinus thrombosis when nonvisualization of a transverse dural sinus is a diagnostic conundrum on phase-contrast MRV and contrast-enhanced studies are contraindicated.

Pigmentary keratitis in pugs in the United Kingdom: prevalence and associated features.

BACKGROUND: Pigmentary keratitis (PK) is commonly recognised in Pugs, but its aetiology is not completely understood. The aim of this study was to determine the prevalence and associated features of PK in Pugs in the United Kingdom (UK). RESULTS: A total of 210 Pugs (420 eyes) were recruited from 12 UK dog shows and social events. The median age of Pugs recruited was 2.50 years (range 0.25-16.25 years). Pigmentary keratitis was detected in 369/420 (87.8%) eyes and in at least one eye 193/210 (91.9%) Pugs, of which 17/193 (8.8%) were affected unilaterally and 176/193 (91.2%) bilaterally. Pigmentary keratitis was typically mild to moderate (46.3 and 49.9% of eyes, respectively). Detection of PK was significantly associated with increased age (P = 0.002) and the presence of medial entropion of the lower eyelid (MELE) (P = 0.001). Severity of PK was significantly associated with the grade of MELE (P < 0.001). There was also a correlation between the presence of limbal pigment and PK (P = 0.036) that warrants further study. CONCLUSIONS: This study estimated a high disease prevalence of PK in UK Pugs, and demonstrated significant associations with age and the presence of MELE. These associations, which have not been previously reported, offer an insight into the underlying pathophysiology of this condition in Pugs. The results encourage further population research, such as prospective longitudinal studies. These findings also support the development of clinical and breeding strategies based on the reduction of MELE and, possibly, limbal pigment.

Associations between neutering and early-onset urinary incontinence in UK bitches under primary veterinary care.

OBJECTIVES: To investigate association between neutering and early-onset urinary incontinence in bitches under primary veterinary care in the UK. MATERIALS AND METHODS: A retrospective cohort study of bitches within VetCompass born between January 1, 2010 and December 31, 2012 that were followed until March 31, 2018. The clinical records were automatically searched and manually validated for incontinence cases. Incidence risk and rate over the study period were calculated. Cox regression modelling separately evaluated the hazard of urinary incontinence and association with neutering: (1) from the date of birth for all bitches, both neutered and entire; and, (2) from the date of neutering for the neutered subset. Other variables considered included breed, bodyweight and veterinary practice group. RESULTS: Overall, 492 bitches were identified with early-onset urinary incontinence from a total of 72,971 included in the study period. Incidence risk was 0.68% (95% confidence intervals 0.62 to 0.74), while incidence rate increased with age. After accounting for confounding factors, increased hazard of early-onset urinary incontinence was identified in: (1) neutered bitches, with the effect increasing with age; and, (2) bitches neutered before 6 months, within the first 2 years following neutering. In both models, increased hazard was additionally associated with increasing bodyweight and breed. CLINICAL SIGNIFICANCE: Neutering itself and early-age neutering (<6 months) are major risk factors for early-onset urinary incontinence. These results should be taken into account in making evidence-based recommendations on neutering and its timing.

Pregabalin for the treatment of syringomyelia-associated neuropathic pain in dogs: A randomised, placebo-controlled, double-masked clinical trial.

Pregabalin is the first-line treatment for neuropathic pain (NeP) in humans. Dogs with Chiari-like malformation and syringomyelia (CM/SM) associated with NeP could benefit from pregabalin. The aim of this study was to evaluate the efficacy of pregabalin for NeP in dogs with CM/SM. Eight dogs with symptomatic CM/SM were included in a double-masked, randomised, crossover placebo-controlled clinical trial. All dogs received anti-inflammatory drugs as base-line treatment during placebo or pregabalin phase of 14±4 days each. Analgesic efficacy was assessed with a daily numerical rating scale (NRS) recorded by dog owners (0-10, 10=worst pain) and quantitative sensory testing at baseline, placebo and pregabalin phases. Blood samples were collected to report pregabalin exposure and to assess renal function. Daily NRS scores recorded by dog owners in the pregabalin group were lower than in the placebo group (P=0.006). Mechanical thresholds were higher with pregabalin compared to baseline or placebo (P=0.037, P<0.001). Cold latency at 15°C was prolonged on the neck and humeri with pregabalin compared to baseline (P<0.001 for both) or placebo (P=0.02, P=0.0001). Cold latency at 0°C was longer on pregabalin compared to baseline and placebo (P=0.001, P=0.004). There was no pregabalin accumulation between first and last dose. This study demonstrates the efficacy of pregabalin for the treatment of NeP due to CM/SM on daily pain scores recorded by dog owners. Pregabalin significantly reduced mechanical hyperalgesia, cold hyperalgesia (0°C) and allodynia (15°C) compared to placebo. Pregabalin was non-cumulative and well tolerated with occasional mild sedation.

Short communication: Pegbovigrastim treatment in vivo does not affect granulocyte ability to migrate to endometrial cells and kill bacteria in vitro in healthy cows.

In periparturient dairy cows, immune suppression, resulting in decreased neutrophil numbers and function, leads to increased susceptibility to postpartum conditions such as mastitis, retained placenta, and metritis. Administration of polyethylene glycol-conjugated bovine granulocyte colony stimulating factor (pegbovigrastim, Imrestor; Elanco Animal Health, Greenfield, IN) 7 d before and within 24 h of calving, effectively improves granulocyte production and function in vivo as well as in milk. A recently developed coculture assay was adapted for use with endometrial epithelial cells to assess the effects of pegbovigrastim application on directed granulocyte migration and bactericidal activity in vitro on a per-cell basis in endometrial cell cultures. Granulocytes from treated and untreated periparturient cows (6 and 5 per group, respectively) were evaluated for their ability to migrate to and kill bacteria after treatment, in context of the infected endometrium. We hypothesized that in addition to increasing the absolute concentration of circulating neutrophil granulocytes, pegbovigrastim treatment in vivo alters the ability of granulocytes to migrate to endometrial cells in vitro. The results clearly show a marked increase in the total concentration of granulocytes and monocytes between the 2 treatment groups as early as 2 d after the first injection, and this increased between the samples taken 2 d after calving. No migratory or killing differences were identified between granulocytes of both groups, suggesting that pegbovigrastim-induced granulocytes were as effective as non-induced cells. This may also be due to the absence of negative energy balance in the study animals and leads us to conclude that the positive effects seen in vivo are most likely based on the larger number of granulocytes present rather than a direct effect of pegbovigrastim treatment on the functionality of cells for the parameters tested in this study.

Diagnostic Utility of Optic Nerve Measurements with MRI in Patients with Optic Nerve Atrophy.

BACKGROUND AND PURPOSE: No MR imaging measurement criteria are available for the diagnosis of optic nerve atrophy. We determined a threshold optic nerve area on MR imaging that predicts a clinical diagnosis of optic nerve atrophy and assessed the relationship between optic nerve area and retinal nerve fiber layer thickness measured by optical coherence tomography, an ancillary test used to evaluate optic nerve disorders. MATERIALS AND METHODS: We evaluated 26 patients with suspected optic nerve atrophy (8 with unilateral, 13 with bilateral and 5 with suspected but not demonstrable optic nerve atrophy) who had both orbital MR imaging and optical coherence tomography examinations. Forty-five patients without optic nerve atrophy served as controls. Coronal inversion recovery images were used to measure optic nerve area on MR imaging. Retinal nerve fiber layer thickness was determined by optical coherence tomography. Individual eyes were treated separately; however, bootstrapping was used to account for clustering when appropriate. Correlation coefficients were used to evaluate relationships; receiver operating characteristic curves, to investigate predictive accuracy. RESULTS: There was a significant difference in optic nerve area between patients' affected eyes with optic nerve atrophy (mean, 3.09 ± 1.09 mm2), patients' unaffected eyes (mean, 5.27 ± 1.39 mm2; P = .008), and control eyes (mean, 6.27 ± 2.64 mm2; P < .001). Optic nerve area ≤ 4.0 mm2 had a sensitivity of 0.85 and a specificity of 0.83 in predicting the diagnosis of optic nerve atrophy. A significant relationship was found between optic nerve area and retinal nerve fiber layer thickness (r = 0.68, P < .001). CONCLUSIONS: MR imaging-measured optic nerve area ≤ 4.0 mm2 has moderately high sensitivity and specificity for predicting optic nerve atrophy, making it a potential diagnostic tool for radiologists.

Atypical myopathy-associated hypoglycin A toxin remains in sycamore seedlings despite mowing, herbicidal spraying or storage in hay and silage.

BACKGROUND: Several pasture management strategies have been proposed to avoid hypoglycin A (HGA) intoxication in horses, but their efficacy has never been investigated. OBJECTIVES: To evaluate the effect of mowing and herbicidal spraying on HGA content of sycamore seedlings and the presence of HGA in seeds and seedlings processed within haylage and silage. STUDY DESIGN: Experimental study. METHODS: Groups of seedlings were mowed (n = 6), sprayed with a dimethylamine-based (n = 2) or a picolinic acid-based herbicide (n = 1). Seedlings were collected before intervention, and at 48 h, 1 and 2 weeks after. Cut grass in the vicinity of mowed seedlings was collected pre-cutting and after 1 week. Seeds and seedling (n = 6) samples processed within haylage and silage were collected. HGA concentration in samples was measured using a validated LC-MS-based method. RESULTS: There was no significant decline in HGA content in either mowed or sprayed seedlings; indeed, mowing induced a temporary significant rise in HGA content of seedlings. HGA concentration increased significantly (albeit to low levels) in grass cut with the seedlings by 1 week. HGA was still present in sycamore material after 6-8 months storage within either hay or silage. MAIN LIMITATIONS: Restricted number of herbicide compounds tested. CONCLUSIONS: Neither mowing nor herbicidal spraying reduces HGA concentration in sycamore seedlings up to 2 weeks after intervention. Cross contamination is possible between grass and sycamore seedlings when mowed together. Mowing followed by collection of sycamore seedlings seems the current best option to avoid HGA toxicity in horses grazing contaminated pasture. Pastures contaminated with sycamore material should not be used to produce processed hay or silage as both seedlings and seeds present in the bales still pose a risk of intoxication.

Epidemiology of race-day distal limb fracture in flat racing Thoroughbreds in Great Britain (2000-2013).

BACKGROUND: A key focus of the racing industry is to minimise the number of race-day distal limb fractures although no studies have identified risk factors for both fatal and non-fatal distal limb fractures. OBJECTIVE: To determine risk factors for race-day distal limb fractures experienced by Thoroughbred racehorses participating in flat racing in Great Britain (GB). STUDY DESIGN: Retrospective cohort. METHODS: Information was collected from all flat racing starts occurring on GB racecourses between 2000 and 2013, including horse, race, course, trainer and jockey data for each horse start and race-day injury data as reported by on-course veterinarians. Associations between exposure variables and cases of distal limb fracture were assessed using mixed-effects logistic regression analyses using data from all starts, and turf starts only. RESULTS: A total of 806,764 starts and 624 cases of distal limb fracture were included, of which 548,571 starts and 379 cases of distal limb fracture occurred on turf surfaces. In both models, increasing firmness of the going, increasing racing distance and horses in their first year of racing were at a higher risk of distal limb fracture while increasing number of previous race starts were protective. Trainer performance was associated with distal limb fracture. Generally, the risk of distal limb fracture increased with increasing horse age. Starts in selling or claiming races or Group 1, Group 3 or claiming races were at higher odds of distal limb fracture in the all starts and turf models, respectively. MAIN LIMITATIONS: Clinical diagnosis of distal limb fracture and all types of distal limb fracture considered as one outcome. CONCLUSIONS: This study confirmed previously identified risk factors for distal limb fracture including going, race distance and number of horse starts. Novel risk factors were related to trainer and horse performance, and race type. Identification of at risk groups will help inform interventions to reduce distal limb fracture occurrence in flat racing horses.

Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares.

Early pregnancy loss (EPL) between days 15-65 after breeding has been shown to occur in 7.9% of equine pregnancies with substantial economical, welfare and safety implications. Whilst maternal age has been recognised as an important risk factor in relation to the incidence of EPL, few other risk factors have been conclusively identified. Further, multivariable data analysis of risk factors for EPL is sparse. A prospective cohort investigation of thoroughbred broodmares in the United Kingdom was conducted over the 2013 and 2014 breeding seasons. Information relating to 28 factors including mare, stallion, pregnancy and therapeutic interventions was collected using questionnaires and entered into a custom-designed Microsoft Access database. Mixed effects logistic regression was used to determine risk factors for EPL, including 'mare' as a random effect to account for repeat pregnancies in the same mare. Stallion, stud and veterinarian were also evaluated as random effects. Variables with a p-value of <0.25 in univariable analysis were taken forward for consideration in the multivariable model which was built using a forward stepwise approach. Data were collected on 2245 pregnancies in 1753 mares. Increasing mare age (OR = 1.11, 95% confidence interval (CI) = 1.04, 1.18, p = 0.001), having had one previous foal (OR = 3.52, 95% CI = 1.56, 7.95, p = 0.002) and presence of uterine cysts (OR = 1.76, 95% CI = 1.07, 2.91, p = 0.03) were all associated with increased odds of EPL following multivariable analysis. Increasing day 15/16 scan vesicle size (OR = 0.24, 95% CI = 0.16, 0.38, p < 0.001) and the use of ovulatory induction agents (OR = 0.31, 95% CI = 0.17, 0.55, p < 0.001) were negatively associated with EPL. Stallion, stud and veterinarian were not significantly associated with EPL. Analysis of a subpopulation of 344 multiple (twin and triplet) pregnancies found that the use of flunixin meglumine at the time of manual reduction of a multiple pregnancy resulted in reduced odds of EPL (OR = 0.34, 95% CI = 0.14, 0.84, p = 0.02). Results from this study can be used by stud farm personnel when assessing their broodmare population and by clinicians when deciding upon therapeutic strategies. Additional work can be focused around these risk factors to further our understanding of the pathophysiology of EPL.