Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Easurement of solids velocity and concentration in a large cold CFB model

This work applies optical probe and particle image velocimetry (PIV) measurements for determining the local characteristics of the solids flow in a CFB riser and discusses benefits and limitations of the two methods. Measurements were carried out in an 8.5 m tall CFB riser with a cross-section of 0.7 m x 0.12 m. The optical probe was used to measure both solids volume fraction and velocity whereas the PIV was limited to solids velocity measurements. In addition, the vertical pressure profile and solids circulation rate were measured by means of pressure transducers. The work demonstrates the challenge of applying detailed solids flow measurements in CFB reactors. Both methods applied are associated with limitations and inaccuracies and it is concluded that a combination of both local measurement methods and the global pressure measurements will improve the interpretation of the solids flow field in CFB risers

Easurement of solids velocity and concentration in a large cold CFB model

This work applies optical probe and particle image velocimetry (PIV) measurements for determining the local characteristics of the solids flow in a CFB riser and discusses benefits and limitations of the two methods. Measurements were carried out in an 8.5 m tall CFB riser with a cross-section of 0.7 m x 0.12 m. The optical probe was used to measure both solids volume fraction and velocity whereas the PIV was limited to solids velocity measurements. In addition, the vertical pressure profile and solids circulation rate were measured by means of pressure transducers. The work demonstrates the challenge of applying detailed solids flow measurements in CFB reactors. Both methods applied are associated with limitations and inaccuracies and it is concluded that a combination of both local measurement methods and the global pressure measurements will improve the interpretation of the solids flow field in CFB risers

Effect of CO2 on oxy-fuel combustion of coal-char particles in a fluidized bed: Modeling and comparison with the conventional mode of combustion

A char combustion model is developed to study the effect of CO2 on the combustion of coarse char particles under oxy-fuel conditions in a fluidized bed (FB). It is a transient one-dimensional model, taking into account the heat and mass transfer from the bed to the particle and the heterogeneous combustion and gasification of char. The model shows good ability to predict the char temperature history measured in our previous work for different combinations of O2/CO2 and O2/N2 with various coal types. Simulations are carried out to establish the role of CO2 in oxy-fuel conversion at different O2 levels, particle sizes, and bed temperatures. The model is used to analyze the relative contribution of carbon in the char consumed by CO2 (gasification) and O2 (combustion), as well as the differences of the peak temperatures and the burnout times in O2/CO2 and O2/N2 for char particles in a commercial FB combustor. The results indicate that the conversion of coarse (mm size) char particles in an oxy-FB is controlled by the diffusion of O2 both in the O2/CO2 and O2/N2 case. The burn-out time decreases with the bed temperature also in both cases. The lower O2 diffusion rate in CO2 compared to N2, is the main reason for the longer burnout time and lower peak temperature found using O2/CO2 at bed temperatures of 1073–1173 K. In that temperature window, the contribution of the CO2-char gasification is limited, being notable only at high bed temperature in O2/CO2, e.g. 1223 K. In such high temperature conditions (rarely expected to be found in commercial coal FBC) the predicted burnout time of a lignite char-particle becomes shorter in O2/CO2 than in O2/N2

The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

The demonstration that the neurosteroid pregnenolone sulfate (PREGS) is active on memory function at both the physiological and pharmacological levels led to us examining in detail the effects of the steroid on spatial working memory by using a two-trial recognition task in a Y-maze, a paradigm based on the natural drive in rodents to explore a novel environment. Dose–response studies in young male adult Sprague–Dawley rats and Swiss mice, after the postacquisition intracerebroventricular injection of steroid, showed an U-inverted curve for memory performance and indicated a greater responsiveness in rats compared with mice. Remarkably, the synthetic (−) enantiomer of PREGS not only also displayed promnesiant activity, but its potency was 10 times higher than that of the natural steroid. Intracerebroventricular coadministration experiments with dl-2-amino-5-phosphonovaleric acid, a competitive selective antagonist of the N-methyl-d-aspartate receptor, abolished the memory-enhancing effect of PREGS, but not that of the PREGS enantiomer, evoking enantiomeric selectivity at the N-methyl-d-aspartate receptor and/or different mechanisms for the promnestic function of the two enantiomers

Oral pharmacokinetically enhanced co-amoxiclav 2000/125 mg, twice daily, compared with co-amoxiclav 875/125 mg, three times daily, in the treatment of community-acquired pneumonia in European adults

OBJECTIVES: Pharmacokinetically enhanced co-amoxiclav 2000/125 mg was designed to achieve high serum concentrations of amoxicillin over the 12 h dosing interval to eradicate Streptococcus pneumoniae with amoxicillin MICs of at least 4 mg/L. METHODS: This randomized, double-blind, double-dummy, multicentre study compared the efficacy and safety of oral co-amoxiclav 2000/125 mg twice daily versus co-amoxiclav 875/125 mg three times daily, for 7 or 10 days, in the treatment of community-acquired pneumonia (CAP). RESULTS: The per-protocol (PP) population at follow-up (Days 18-39) comprised 114 patients receiving co-amoxiclav 2000/125 mg and 116 receiving co-amoxiclav 875/125 mg. Clinical success at follow-up (primary efficacy endpoint) in the clinical PP population was 94.7% (108/114) for co-amoxiclav 2000/125 mg versus 88.8% (103/116) for co-amoxiclav 875/125 mg [treatment difference (TD) = 5.9%, 95% CI: 1.1, 13.0]. Bacteriological success in the bacteriology PP population at follow-up was 85.0% (17/20) for co-amoxiclav 2000/125 mg versus 77.3% (17/22) for co-amoxiclav 875/125 mg (TD = 7.7%, 95% CI: 15.8, 31.2). Penicillin-resistant S. pneumoniae (PRSP) were isolated in three patients (including two with bacteraemia) in the co-amoxiclav 2000/125 mg group (amoxicillin MICs 8 mg/L, penicillin MICs 4 mg/L) and one in the comparator group; all were clinical and bacteriological successes. Co-amoxiclav 2000/125 mg and co-amoxiclav 875/125 mg were associated with adverse events leading to withdrawal in 6.3% and 6.2% of patients, respectively. CONCLUSIONS: Co-amoxiclav 2000/125 mg twice daily was at least as effective clinically as co-amoxiclav 875/125 mg three times daily in the treatment of CAP. Although few patients in this study had PRSP infection, 3/3 were successfully treated with co-amoxiclav 2000/125 mg