No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a.

BackgroundNo evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS).ObjectiveThe objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status.MethodsNEDA was assessed in a modified intent-to-treat population (n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β-1a; 44 μg).ResultsNEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% (p < 0.001), from Week 0‒24 by 33% (p < 0.001) and from Week 24‒96 by 72% (p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001).ConclusionSuperior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab

Efficacy of daclizumab beta versus intramuscular interferon beta-1a on disability progression across patient demographic and disease activity subgroups in DECIDE.

BACKGROUND: Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments. OBJECTIVE: Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE. METHODS: Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics. RESULTS: Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS progression (HR, 0.80; 95% CI, 0.67-0.95), and odds of clinically meaningful worsening in MSIS-29 PHYS (odds ratio, 0.76; 95% CI, 0.60-0.95) versus IM interferon beta-1a. Point estimates showed trends favoring daclizumab beta over IM interferon beta-1a across several patient subgroups for all three outcome measures. CONCLUSION: Daclizumab beta showed consistent benefit versus IM interferon beta-1a across measures assessing patient disability/function and across a range of clinical baseline characteristics in patients with relapsing-remitting MS

Vliv četnosti přihrnování na chování zvířat, příjem sušiny a dojivost dojnic

This study evaluated the effect of different feed pushing-up frequencies on the behavior, dry matter intake and milk production of dairy cows in the first lactation. In each monitoring, 32 - 37 dairy cows of Czech spotted cattle at the peak of lactation were represented. After the feed was delivered to cows, the feed was pushed-up 2, 3, 4, 5, or 6 times in 5 different frequencies within 12 hours. Each frequency was monitored for 1 month in four repetitions. The behavior of dairy cows during feeding was monitored for 15 minutes after the feed delivery and after each food pushing-up. We evaluated how often the dairy cows came to the feeding table, how they used mixed ration and milk production. The frequency of feed pushing-ups has shown an effect on the dairy cow\u27s milk yield. As a result of the 2, 3, 4, 5 and 6 feed pushing-up frequencies, the average milk production per cow per day was 24.52; 25.84; 25.48; 25.78; 26.03 kg. Also feed conversion increased with the frequency of feed pushing-ups to 1.22; 1.29; 1.25; 1.30 and 1.30 kg of milk from 1 kg of received dry matter. TMR dry matter utilization increased by 1% on average.Tato studie hodnotila vliv různých četností přihrnutí krmiva na chování dojnic, příjem sušiny a mléčnou produkci dojnic na první laktaci. V každém sledování bylo zastoupeno 32 - 37 dojnic českého strakatého skotu na vrcholu laktace. Bylo zvoleno 5 frekvencí přihrnutí krmiva během 12 hodin od jeho založení. Počet přihrnutí byl 2, 3, 4, 5, 6. Doba sledování každé frekvence byla 1 měsíc ve čtyřech opakováních. Chování dojnic během krmení bylo sledováno po dobu 15 minut od založení krmiva a každého přihrnutí. Hodnocena byla návštěvnost dojnic u krmného stolu, využití směsné krmné dávky dojnicí a produkce mléka. Frekvence přihrnování krmiva prokázala vliv na mléčnou užitkovost dojnice. Průměrná produkce mléka na kus a den činila 24,52; 25,84; 25,48; 25,78; 26,03 kg pro frekvence přihrnutí 2, 3, 4, 5 a 6. Konverze krmiva se zvýšila s četností přihrnutí na 1,22; 1,29; 1,25; 1,30; 1,30 kg mléka z 1 kg přijaté sušiny. Využití sušiny TMR se v průměru zvýšilo o 1%

The feed push-up as a factor influencing health of dairy cows

The effect of feed push-up has already been proven in several studies, so this topic can be considered one of the main points that helps improve the health status of dairy cattle. This study aimed to determine how the frequency of feed push-ups influences the health status of udder (mastitis), somatic cell counts, and reproduction. The effect of feed push-up on mastitis, the somatic cell counts, and the conception of dairy cows was evaluated. The feed was pushed-up at a frequency of 2x, 3x, 4x, 5x, and 6x a day for one calendar month. The effect on the number of dairy cows treated with mastitis was insignificant (P ≥ 0.05). The lowest number of cows with mastitis was found when feed was pushed-up five times daily. The effect on the somatic cell counts was insignificantly, too (P ≥ 0.05). The worst milk quality was found in the experimental group, which had a frequency of push-up 5x/day. However, it has been shown that the frequency of food push-up positively affected the conception rate in dairy cows (P < 0.001)

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen