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.
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.
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 β-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 β-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 β-adrenergic challenge, have therapeutic implications for ageing LQTS patients.
Currently, efficacy of a new factor concentrate is mostly judged by its ability to achieve haemostasis after a bleeding episode. However, in patients on prophylaxis, the effectiveness in preventing bleeds, and thus joint damage, is most important. An albumin-free recombinant factor VIII (FVIII) concentrate was introduced in the Netherlands in 2004. In this study, the efficacy of a new recombinant plasma/albumin-free FVIII concentrate (rAHF-PFM, Advate) was assessed by comparing bleeding frequency and factor consumption before and after switching to the new product, on both prophylactic and on-demand treatment. Eighty-two previously treated haemophilia A patients with at least 1-year clinical follow-up were included in this study. Data on 410 patient-years were analysed, including 165 patient-years on other clotting factor products, and 245 patient-years on the new concentrate. In total, 19 628 368 IU of other factor concentrates were administered, to treat 839 bleeds, including 578 joint bleeds and cover 104 years of prophylactic treatment. For rAHF-PFM 33 082 250 IU FVIII, were used to treat 1144 bleeds, including 734 joint bleeds and cover 175 years of prophylactic treatment. No inhibitors, seroconversions or other serious adverse events were observed. Annual FVIII consumption per kg and annual number of joint bleeds before and after switching to the new albumin-free recombinant factor concentrate were similar in all patients. In conclusion, rAHF-PFM is equally effective as other clotting factor concentrates for prophylactic treatment in severe haemophilia.
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.
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