External validation of a collar-mounted triaxial accelerometer for second-by-second monitoring of eight behavioural states in dogs.

Early detection of disease by an animal owner may motivate them to seek early veterinary advice. Presentation before a more advanced clinical manifestation is evident could lead to more effective treatment and thus benefit the animal's health and welfare. Accelerometers are able to detect changes in specific activities or behaviours, thus indicating early signs of possible adverse health events. The objective of this validation study was to determine whether the detection of eight behavioural states: walk, trot, canter/gallop, sleep, static/inactive, eat, drink, and headshake, by an accelerometer device was sufficiently accurate to be useful in a clinical setting. This fully independent external validation estimated the accuracy of a specific triaxial, collar-mounted accelerometer on a second-by second basis in 51 healthy dogs of different breeds, aged between 6 months and 13 years, weighing >10 kg. The overall diagnostic effectiveness was estimated as: % record correctly classified of > 95% in walk, trot, canter/gallop, eat, drink and headshake and >90% in sleep and static/inactive. The positive predictive values ranged from 93-100%, while the negative predictive values ranged from 96-100%, with exception of static/inactive (86%).This was probably because dogs were placed in unfamiliar kennels where they did not exhibit their typical resting behaviour. The device is worn on a collar, making its use feasible for anyone wanting to monitor their dog's behaviour. The high accuracy in detecting various kinds of behaviour appears promising in assessing canine health and welfare states.

The effects of ageing and adrenergic challenge on electrocardiographic phenotypes in a murine model of long QT syndrome type 3.

Long QT Syndrome 3 (LQTS3) arises from gain-of-function Nav1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to ß-adrenergic agents. We investigated for independent and interacting effects of age and Scn5a+/ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following ß-agonist challenge, and upon fibrotic change. Prolonged ventricular recovery was independently associated with Scn5a+/ΔKPQ and age. Ventricular activation was prolonged in old Scn5a+/ΔKPQ mice (p = 0.03). We associated Scn5a+/ΔKPQ with increased atrial and ventricular fibrosis (both: p < 0.001). Ventricles also showed increased fibrosis with age (p < 0.001). Age and Scn5a+/ΔKPQ interacted in increasing incidences of repolarisation alternans (p = 0.02). Dobutamine increased ventricular rate (p < 0.001) and reduced both atrioventricular conduction (PR segment-p = 0.02; PR interval-p = 0.02) and incidences of repolarisation alternans (p < 0.001) in all mice. However, in Scn5a+/ΔKPQ mice, dobutamine delayed the changes in ventricular repolarisation following corresponding increases in ventricular rate. The present findings implicate interactions between age and Scn5a+/ΔKPQ in prolonging ventricular activation, correlating them with fibrotic change for the first time, adding activation abnormalities to established recovery abnormalities in LQTS3. These findings, together with dynamic electrophysiological responses to ß-adrenergic challenge, have therapeutic implications for ageing LQTS patients.

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multi-country study.

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named 'bovine neonatal pancytopenia' (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0-280.1). This was also the case for the practices of feeding calves colostrum from the calf's own dam (OR 2.0; 95% CI: 1.1-3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9-8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves.

Outcome in moderate haemophilia.

BACKGROUND: Moderate haemophilia is the rarest form of haemophilia. This study aims to assess short- and long-term outcome, including its association with treatment, in patients with moderate haemophilia. MATERIAL AND METHODS: Seventy-five patients with moderate haemophilia (1-5% factor VIII/ factor IX activity), without a history of inhibitors, treated at the van Creveldkliniek, Utrecht (NL) were included in the study. Life-long data on bleeding and treatment were collected. Joints were evaluated using the Haemophilia Joint Health Score. Adults completed questionnaires on activity (HAL) and quality of life (SF-36, EQ5D). RESULTS: The median age of the patients was 37 years (IQR 23-52 years) and haemophilia A was diagnosed in 89%. Bleeding frequency was low: the median annual bleeding rate was 2.0 bleeds/ year (IQR 0.8-3.7 bleeds/year), including a median of 0 joint bleeds/year (IQR 0.8-3.7 bleeds/year). Joint function was good: 82% scored<10 out of 126 points of the Haemophilia Joint Health Score (HJHS). Nevertheless, 29% of patients with moderate haemophilia had a history of prophylaxis, because of a high bleeding frequency. Median age at first joint bleed was 4.8 years (IQR 3.5-8.5). Use of prophylaxis was more associated with age at first joint bleed (P<0.01) than with baseline factor activity (P=0.12). Most patients (52%) who suffered their first joint bleed before the age of 5 years required prophylaxis later in life. DISCUSSION: The majority of patients with moderate haemophilia have few bleeds and complications; however, a considerable subset of patients with a more severe bleeding pattern need prophylactic treatment. These latter patients may be identified by the onset of joint bleeding before the age of 5 years.

Calf-level factors associated with bovine neonatal pancytopenia--a multi-country case-control study.

Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval - ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam's milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows' colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam's milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.

Turning severe into moderate haemophilia by prophylaxis: are we reaching our goal?

BACKGROUND: Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH. MATERIAL AND METHODS: The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970-1995. RESULTS: The median age of the patients was 24 years (IQR 18-30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2-6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8-13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR =0.8-3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR =0-1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2,120 IU/kg; IQR 1,514-2,768), was higher than that of MH patients (median 133 IU/kg; IQR 49-468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3-15) vs a median of 2 points, IQR 0-6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population. DISCUSSION: When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.