Many studies in the field of haemophilia and other coagulation deficiencies require analyses of bleeding frequencies. In haemophilia, the association of bleeding frequency with factor VIII (FVIII) activity levels is known from experience, but significant results are lacking. Bleeding frequencies in haemophilia are highly skewed count data, with large proportions of zeros. Both the skewness and the high amount of zeros pose a problem for standard (linear) modelling techniques. This study investigated the optimal analysing strategy for bleeding data by using the association of residual clotting factor level and number of joint bleeds in moderate and mild patients treated on demand as example. In total, 433 patients with moderate (27%) and mild (73%) haemophilia A treated on demand were included in this study. One year of self-reported data on joint bleed frequency and baseline clotting factor activity were analysed using Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial distributions. Multivariate regression analysis using negative binomial distribution provided the optimum data analytical strategy. This model showed 18% reduction [Rate ratio (RR) 0.82; 95%confidence interval (CI) 0.77-0.86] of bleeding frequency with every IU dL -1 increase in residual FVIII activity. The actual association is expected to be higher because of exclusion (30 out of 463 patients) of patients on prophylaxis (baseline FVIII levels 0.01-0.06 IU mL )1 ). The best way to analyse low frequency bleeding data is using a negative binomial distribution.

The classification of haemophilia originates from 1950s and has been adopted unchallengedly by the ISTH in 2001. The aim of this study was: does the current classification compare onset of bleeding and age at first treatment, as well as annual joint bleeding frequency according to baseline FVIII activity? Data on age and reason of diagnosis, onset of treatment, onset of bleeding and bleeding frequency from 411 patients with haemophilia A born after 1970 were collected. Data were analysed according to base-line FVIII activity levels. Age at diagnosis, onset of bleeding and start of treatment according to FVIII activity were compared with the current classification. Overall, the distinction between severe and non-severe haemophilia was clear. The distinction between mild and moderate haemophilia was more difficult, mostly due to the wide variability in the group of patients with moderate haemophilia. Patients with severe haemophilia experienced their milestones like diagnosis, first treatment and joint bleed earliest, mostly as infants aged 0-3 years, whereas patients with moderate haemophilia reached these milestones around toddler age, 2-7 years, and patients with mild haemophilia reached them when they were in elementary school, around the ages of 5-14 years. This study confirms the clinical distinction between severe and non-severe haemophilia A. However, the group of moderate haemophilia patients showed a wide variability, warranting close follow-up and individualized treatment.

The goal of dry cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antibiotics has become questionable. This study evaluated selective DCT in 1,657 cows with low somatic cell count (SCC) at the last milk recording before drying off in 97 Dutch dairy herds. Low SCC was defined as <150,000 cells/mL for primiparous and <250,000 cells/ mL for multiparous cows. A split-udder design was used in which 2 quarters of each cow were treated with dry cow antibiotics and the other 2 quarters remained as untreated controls. The effect of DCT on clinical mastitis (CM), bacteriological status, SCC, and antibiotic use were determined at the quarter level using logistic regression and chi-squared tests. The incidence rate of CM was found to be 1.7 times (95% confidence interval = 1.4-2.1) higher in quarters dried off without antibiotics as compared with quarters dried off with antibiotics. Streptococcus uberis was the predominant organism causing CM in both groups. Somatic cell count at calving and 14 d in milk was significantly higher in quarters dried off without antibiotics (772,000 and 46,000 cells/mL, respectively) as compared with the quarters dried off with antibiotics (578,000 and 30,000 cells/mL, respectively). Quarters with an elevated SCC at drying off and quarters with a positive culture for major pathogens at drying off had a higher risk for an SCC above 200,000 cells/mL at 14 d in milk as compared with quarters with a low SCC at drying off and quarters with a negative culture for major pathogens at drying off. For quarters that were culture-positive for major pathogens at drying off, a trend for a higher risk on CM was also found. Selective DCT, not using DCT in cows that had a low SCC at the last milk recording before drying off, significantly increased the incidence rate of CM and SCC. The decrease in antibiotic use by drying off quarters without DCT was not compensated by an increase in antibiotic use for treating CM. Total antibiotic use related to mastitis was reduced by 85% in these quarters.

Although outcome in moderate haemophilia is generally in between severe and mild haemophilia, moderate haemophilia patients reported a substantial burden of disease, and for more than 25% of patients with moderate haemophilia long term prophylaxis was implemented because of frequent bleeds.