Reductie stofemissie bij vleeskuikens door aanbrengen oliefilm = Reduction of dust emission from broilers by application of an oil film

The effect of application of an oil film on bedding on dust reduction in a broiler house was studied. The system proved to be effectiv

Phase 1 study of chemoradiotherapy combined with nivolumab +/- Ipilimumab for the curative treatment of muscle-invasive bladder cancer

Background: Muscle-invasive bladder cancer (MIBC) has a poor prognosis. Chemoradiotherapy (CRT) in selected patients has comparable results to radical cystectomy. Results of neoadjuvant immune checkpoint inhibitors (ICIs) before radical cystectomy are promising. We hypothesize that ICI concurrent to CRT (iCRT) is safe and may improve treatment outcomes. Objective: To determine the safety of iCRT for MIBC. Design, setting, and participants: This multicenter, phase 1b, open-label, dose-escalation study determined the safety of CRT with three ICI regimens in patients with nonmetastatic (T2-4aN0-1) MIBC. Twenty-six patients received mitomycin C/capecitabine and 20 x 2.75 Gy to the bladder. Tolerability was evaluated in a cohort of up to ten patients. If two or fewer out of the first six patients or three or fewer of ten patients experienced dose-limiting toxicity (DLT), accrual continued in the next cohort. Intervention: Patients received nivolumab 480 mg (NIVO480), nivolumab 3 mg/kg and ipilimumab 1 mg/kg (NIVO3 + IPI1), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg (IPI3 + NIVO1). Outcome measurements and statistical analysis: The primary endpoint was safety. Secondary objectives were response rate, disease-free survival, metastatic-free survival (MFS), and overall survival (OS). Results and limitations: In the NIVO480 cohort, no patients experienced DLT. The NIVO3 + IPI1 2 patients experienced DLT, thrombocytopenia (grade 4), and asystole (grade 5). IPI3 + NIVO1 was discontinued after three out of six patients experienced DLT. Clinically significant adverse events (AEs) of grade >= 3 occurred in zero, three, and five patients in the NIVO480, NIVO3 + IPI1, and IPI3 + NIVO1 groups, respectively. The most common AEs were immune related and gastrointestinal. MFS and OS were 90% at 2 yr for NIVO480 and 90% at 1 yr for NIVO3 + IPI1. Limitations include the absence of a centralized pathology and radiology review, and a lack of biomarker analysis. Conclusions: In this dose-finding study of iCRT, the regimens of nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg have acceptable toxicity. Patient summary: We tested the safety of a new bladder-sparing treatment modality for muscle-invasive bladder cancer patients, combiningimmunecheckpoint inhibitors simultaneously with chemoradiotherapy. We report that two regimens, nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg, are safe and can be used in phase 3 trials

Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378]

BACKGROUND: Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now. METHODS: One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 × 10(6 )copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000–1200 mg / day), 6 months ribavirin monotherapy (1000–1200 mg / day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. RESULTS: At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01). DISCUSSION: This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts

Comparison of performance, health and welfare aspects between commercially housed hatchery-hatched and on-farm hatched broiler flocks

On-farm hatching systems for broiler chicks are increasingly used in practice. We studied whether or not performance, health and welfare aspects differed between commercial flocks hatched on-farm or in a hatchery (control). In two successive production cycles on seven farms, a total of 16 on-farm hatched flocks were paired to 16 control flocks, housed at the same farm. Paired flocks originated from the same batch of eggs and were subjected to similar on-farm management. On-farm hatched and control flocks only differed with respect to hatching conditions, with on-farm hatched flocks not being exposed to, for example, chick handling, post-hatch feed and water deprivation and transport, in contrast to control flocks that were subjected to standard hatchery procedures, subsequently transported and placed in the poultry house. Day-old chick quality (navel and hock scores), 1st week mortality, total mortality, BW at day (d) 0, d7 and at depopulation, and (total) feed conversion ratio were determined. Prevalence of footpad dermatitis, hock burn, breast discoloration/blisters and cleanliness, litter quality and gait score were determined at d21 of age and around depopulation (d39 on average). Gross pathology and gut morphology were examined at depopulation age in a sample of birds of five flocks per treatment. On-farm hatching resulted in a higher BW at d0 (=5.4 g) and d7 (=11.5 g) (Pst week and total mortality, and feed conversion ratio at slaughter age were similar for both on-farm hatched and control flocks. On-farm hatched flocks had less footpad dermatitis (P=0.05), which indicated a better welfare. This was likely related to a tendency for better litter quality in on-farm hatched flocks at 21 days of age in comparison to control flocks (P=0.08). No major differences in gross pathology or in intestinal morphology at depopulation age were found between treatments. In conclusion, on-farm hatching resulted in better 1st week broiler performance and better welfare compared to conventional hatching in a hatchery.</p

Diet dilution and feeding frequency have only minor effects on the behaviour of broiler breeder pullets

During the rearing period, broiler breeders are feed restricted to prevent the negative impact of fast growth and high body weight on health and reproduction. Feed restriction causes frustration and stress, resulting in stereotypic pecking and hyperactivity. Nutritional strategies have the potential to reduce these welfare issues. Using a 2 × 2 factorial completely randomized block design, pullets were fed with two diet densities and two feeding frequencies during rearing. From 3–23 weeks of age (WOA), pullets received either a standard control diet (CON) or a 16% diluted diet (DIL) containing oat hulls. These diets were provided either once (FO) or twice (FT) a day. After 23 WOA, all pullets received the same standard layer diet once a day. Home pen behaviour was observed by scan sampling at 5, 10, 15, 20, 30 and 39 WOA over eight observation sessions. Furthermore, pullets were subjected to Novel Food Tests (12 and 17 WOA) and Novel Object Tests (5, 10, 15 and 20 WOA). Minor treatment effects were found for foraging and sitting behaviour that varied with age during rearing. Feeding frequency influenced the behavioural patterns of all home pen behaviours (P < 0.001; object pecking P = 0.034), while diet dilution only affected the expression of foraging behaviour during the day (P = 0.007). In all treatment groups, many pullets were observed standing and walking in anticipation of the first meal. After the first meal and before the second meal, more FT pullets were observed standing and walking, while during and after the second meal more FO pullets were observed sitting and performing comfort behaviour. Feeding twice a day resulted in lower daily peaks in drinking behaviour. In the laying period, when all birds received the same layer diet at the same frequency, those who were fed twice daily during rearing foraged more than those who were fed once (P = 0.028) and birds that received a diluted diet during rearing tended to drink more than birds that received the control diet (P = 0.083). Few treatment effects were found in the Novel Food and Novel Object Tests, indicating that diet dilution and/or feeding frequency, as applied here, did not affect fearful behaviour or the motivation to explore. In conclusion, this study showed that neither diet dilution, twice-daily feeding, or the combination of these, improved broiler breeder welfare during rearing and laying. Some changes in the pattern of home pen behaviour were found that indicated a response to the frequency of food provisioning

Covered stents versus Bare-metal stents in c hronic atherosclerotic Gastrointestinal Ischemia (CoBaGI): study protocol for a randomized controlled trial

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI.Methods/design: The CoBaGI trial is a randomized controlled, parallel-group, patient-and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months.Discussion: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis.Vascular Surger