Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Impact of low-trans fat compositions on the quality of conventional and fat-reduced puff pastry

Four vegetable fat blends (FBs) with low trans-fatty acid (TFA ≤ 0.6 %) content with various ratios of palm stearin (PS) and rapeseed oil (RO) were characterised and examined for their application in puff pastry production. The amount of PS decreased from FB1 to FB4 and simultaneously the RO content increased. A range of analytical methods were used to characterise the FBs, including solid fat content (SFC), differential scanning calorimetry (DSC), cone penetrometry and rheological measurements. The internal and external structural quality parameters of baked puff pastry were investigated using texture analyser equipped with an Extended Craft Knife (ECK), VolScan and C-Cell image system. Puff pastry containing FB1 and FB2 achieved excellent baking results for full fat and fat-reduced puff pastry; hence these FBs contained adequate shortening properties. A fat reduction by 40 % using FB2 and a reduction of saturated fatty acids (SAFA) by 49 %, compared to the control, did not lead to adverse effects in lift and specific volume. The higher amount of RO and the lower SAFA content compared to FB1 coupled with the satisfying baking results makes FB2 the fat of choice in this study. FB3 and FB4 were found to be unsuitable for puff pastry production because of their melting behaviour

Application of sourdough in the production of fat- and salt-reduced puff pastry

Sourdough (SD), as a natural ingredient, has the highly promising potential to compensate the effect of salt reduction on flavour and the consequent influence on further sensory characteristics in bakery products. The objective of this research was to determine the impact of SD (5, 10 and 20% flour basis) on the structure, flavour and quality characteristics of puff pastry with reduced fat (-40%) and salt (-30%) content (RFRS) as well as the rheological properties of the resulting dough. A range of empirical rheological tests was carried out including dough extensibility, dough stickiness and GlutoPeak test. Subsequently, the baked puff pastry quality was investigated using a VolScan, texture analyser, C-Cell and sensory analysis. SD addition significantly changed rheological properties of the basic dough reduced in fat and salt as well as a number of major quality characteristics for the resulting puff pastry. Dough resistance decreased and dough stickiness increased (p &lt; 0.05). Gluten formation was delayed for the higher in salt control and accelerated upon salt reduction as well as increasing levels of SD incorporation. Furthermore, SD addition weakened the gluten network. To some extent, RFRS containing SD were significantly enhanced in texture. Peak firmness of RFRS with SD was significantly decreased when compared to RFRS without SD. Furthermore, the specific volume of RFRS with 5 and 10% SD was significantly higher than for RFRS containing no SD. Finally, supported by a sensory study, the flavour and texture of reduced fat and salt pastry were distinctly improved by 10% SD addition

Measurement of b jet shapes in proton-proton collisions at s=5.02 TeV

We present the first study of charged-hadron production associated with jets originating from b quarks in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data sample used in this study was collected with the CMS detector at the CERN LHC and corresponds to an integrated luminosity of 27.4 pb(-1). To characterize the jet substructure, the differential jet shapes, defined as the normalized transverse momentum distribution of charged hadrons as a function of angular distance from the jet axis, are measured for b jets. In addition to the jet shapes, the per-jet yields of charged particles associated with b jets are also quantified, again as a function of the angular distance with respect to the jet axis. Extracted jet shape and particle yield distributions for b jets are compared with results for inclusive jets, as well as with the predictions from the pythia and herwig++ event generators