Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial.

OBJECTIVE: To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). METHODS: This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. RESULTS: In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). CONCLUSIONS: Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. TRIAL REGISTRATION NUMBER: NCT00988221.

Factors associated with body temperature of healthy Holstein dairy cows during the first 10 days in milk.

In this prospective observational study rectal and vaginal temperature of 82 (26 primiparous, 56 multiparous) early post-partum healthy dairy cows that calved without intervention within 3 months and did not show clinical signs of infectious and metabolic diseases were continuously measured and evaluated for associations with plausible factors during the first 10 days in milk (DIM). During May, June and July mean (±SD) temperature humidity index (THI) was 60·1±5; 66·8±5·6 and 74·2±4·3, respectively. Environmental conditions had a negligible effect on body temperature (BT) during May (P<0·05). During June and July, however, the ambient temperature and THI influenced BT (P<0·05). Furthermore, plausible factors like parity, DIM, months and time of day had an effect on BT (P<0·05). Overall, primiparous cows demonstrated 0·2°C greater BT during the first 10 DIM than multiparous cows. The effect of parity, however, on BT varied between DIM according to month (P<0·001). During this 3-month study period all cows demonstrated BT rhythms; however, the amplitude of BT increased from May to July (0·3 to 0·7°C). A greater proportion of the vaginal temperature measurements exceeded a threshold tested (≥39·5°C) during July (46·8%) than in June (33·9%) and May (19·3%). Overall the percentage of BT values above a threshold of ≥39·5°C was lower during the period 6.00-10.00 compared with the remaining 20 h (P<0·05). Therefore this study concluded that the BT of healthy post-partum dairy cows during the period 1-10 DIM post partum is greater compared with the reference range of 38·6 to 39·5°C reported by others and is influenced by parity, DIM, time of day and THI. When the association between BT and THI increased the reliability of threshold levels of BT (≥39·5°C) decreased.

In vitro susceptibility of ceftiofur against Streptococcus equi subsp zooepidemicus and subsp equi isolated from horses with lower respiratory disease in Europe since 2002.

In vitro activity of ceftiofur and six other antimicrobial agents was evaluated against 79 Streptococcus equi subsp zooepidemicus isolates collected from horses with respiratory disease in Europe during 2007 and 2008. In addition, the in vitro activity of ceftiofur and other antimicrobial drugs was assessed against 59 S. equi subsp zooepidemicus and 49 S. equi subsp equi isolates collected by veterinary diagnostic laboratories in Europe from 2002 to 2006. The lowest concentration of ceftiofur that inhibited the growth of 90% of the isolates (MIC90) was 0.12 microg/ml, with the Clinical Laboratory Standards Institute-approved susceptible breakpoint set at ≤ 0.25 microg/ml for ceftiofur against S. equi subsp zooepidemicus. The MIC90 values remained consistent when comparing the isolates collected from diagnostic laboratories or from the field study.