MSD (Austria)

The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2-8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26-2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum β-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.

ObjectiveTo analyze real-world evidence on work productivity and daily activity impairment (WPAI) and health-related quality of life (HRQoL) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients treated with golimumab in Austria.MethodsThis was a prospective, non-interventional, multi-center study conducted in RA, PsA and axSpA patients initiating golimumab between April 2016 and May 2020 in 40 centers in Austria. WPAI, HRQoL (RAQoL, ankylosing spondylitis (AS)QoL and PsAQoL) questionnaires and disease activity (Clinical Disease Activity Index, CDAI, in RA and PsA; Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, in axSpA) were assessed at baseline and months 3, 6, 12, 18, and 24. Association between WPAI and disease activity was tested using linear regression.ResultsWe enrolled 233 patients (RA, n = 95; axSpA, n = 69; PsA, n = 69), 110 patients were followed up to month 24. Mean age was 50.2 ± 14.2 years; 64% were female. Disease activity decreased from baseline to month 24 (RA: CDAI −24.3 ± 13.5; axSpA: BASDAI −4.4 ± 2.1, and PsA: CDAI −21.7 ± 8.5, p < 0.0001, each). Total work productivity impairment (TWPI), activity impairment and presenteeism subscores continuously decreased throughout month 24 in all indications: RA (−58.3 ± 23%, −62.6 ± 23.8% and −61.7 ± 23.3%, respectively as compared to baseline; p < 0.0001, each), axSpA (−34.4 ± 38.3%, p = 0.0117; −60.9 ± 25.9%, and −43.8 ± 26.6%, respectively, p ≤ 0.0001 both) and PsA (−35.8 ± 43.7%, p = 0.0186; −52.3 ± 25.4%, p < 0.0001; and −43.3 ± 33.5%, p = 0.0007, respectively). Absenteeism scores decreased only in RA patients (−9.2 ± 24.9%, p = 0.0234). HRQoL improved between baseline and month 24 (RAQoL: −12.6 ± 7.5; ASQoL: −8.0 ± 4.3; PsAQoL; −8.3 ± 6.4, p < 0.0001, each). TWPI, presenteeism and activity impairment strongly associated with disease activity throughout the study.ConclusionsThis real-world study confirms the benefit of golimumab on work productivity/daily activity impairment in Austrian RA, PsA, and axSpA patients.

We discuss an experiment to investigate neutrino physics at the LHC in Run 3, with emphasis on tau flavour. As described in our previous paper [arXiv:1903.06564v1], the detector can be installed in the decommissioned TI18 tunnel, about 480 m downstream the ATLAS cavern, after the first bending dipoles of the LHC arc. In that location, the prolongation of the beam Line-of-Sight from Interaction Point IP1 to TI18 traverses about 100 m of rock. The detector intercepts the intense neutrino flux, generated by the LHC beams colliding in IP1, at large pseudorapidity eta, where neutrino energies can exceed a TeV. This paper focuses on optimizing global features of the experiment, like detector mass and acceptance. Since the neutrino-nucleon interaction cross section grows almost linearly with energy, the detector can be light and still collect a considerable sample of neutrino events; in the present study it weighs less than 3 tons. The detector is positioned off the beam axis, slightly above the ideal prolongation of the LHC beam from the straight section, covering 7.4 < eta < 9.2. In this configuration, the flux at high energies (0.5-1.5 TeV and beyond) is found to be dominated by neutrinos originating directly from IP1, mostly from charm decays, of which about 50% are electron neutrinos and about 5% are tau neutrinos. The contribution of pion and kaon decays to the muon neutrino flux is studied by means of simulations that embed the LHC optics and found small at high energies. The above studies indicate that with 150 /fb of delivered LHC luminosity in Run 3 the experiment can record a few thousand very high energy neutrino charged current interactions and over 50 tau neutrino charged current events.

OBJECTIVE: To assess adherence to, and effectiveness and convenience of, treatment with subcutaneous (sc) interferon (IFN) beta-1a 44 or 22 mcg three times weekly in patients with relapsing multiple sclerosis (RMS) using the RebiSmart™ electronic, multidose, autoinjector. BACKGROUND: Patients with MS and poor adherence have a higher risk of relapse than adherent patients. Administration of IFN beta-1a with an autoinjector has been reported to improve the injection experience and increase adherence. RebiSmart™ is a CE-certified medical device. DESIGN/METHODS: European, multicentre, observational study. Inclusion criteria: 18-65 years-of-age with RMS; EDSS score ≤6; MS-treatment naïve or sc IFN beta-1a administered by RebiSmart™ for ≤8 weeks. Primary endpoint was cumulative adherence recorded by RebiSmart™. RESULTS: The safety population comprised 912 patients, 77.4% of whom completed the month-12 visit; the most common reason for early discontinuation (ED) was adverse reaction (5.5%), most frequently at the injection site (1.3%). At month 12/ED, mean(±SD) cumulative adherence per patient was 97.0±7.3% and 260 patients (31.6%) had missed injections since the last visit (mean 7.0±13.8/patient). The most common reason for missed injection was ‘forgot to inject’ (37.0%). At month 12/ED, 79.5% of patients were relapse-free and the mean(±SD) annualised relapse rate was 0.3±0.8 versus 1.9±1.5 at baseline. In a subgroup of 720 patients with complete data, a significantly higher proportion treated with high-dose (蠅120 mcg/week; N=227) versus low dose IFN beta-1a (<120 mcg/week; N=293) were relapse free at month 6 (92.5% vs. 86.7%; p=0.0451), with a non-significant trend (82.1% vs. 76.6%) at month 12/ED. No unknown safety issues were detected. Of 353 patients who completed a convenience questionnaire, 68.3% found injecting with RebiSmart™ ‘very easy’. CONCLUSIONS: Patients with RMS self-injecting sc IFN beta-1a with RebiSmart™ had excellent adherence, which was associated with good clinical outcomes and no unexpected safety issues. Patients rated the convenience of RebiSmart™ positively. Study Supported by: This study was supported by Merck Serono SA Geneva, Switzerland, a subsidiary of Merck KGaA, Darmstadt, Germany