Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with placebo ...in patients with active, mild-to-moderate ulcerative colitis (UC).
Patients were randomised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg, or Entocort EC 9 mg (budesonide controlled ileal-release capsules; reference arm) or placebo once daily for 8 weeks. The primary endpoint was combined clinical and endoscopic remission, defined as UC Disease Activity Index score ≤1 with a score of 0 for rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ≥1-point reduction in endoscopic index score from baseline.
410 patients were evaluated for efficacy. Combined clinical and endoscopic remission rates with budesonide MMX 9 mg or 6 mg, Entocort EC and placebo were 17.4%, 8.3%, 12.6% and 4.5%, respectively. The difference between budesonide MMX 9 mg and placebo was significant (OR 4.49; 95% CI 1.47 to 13.72; p=0.0047). Budesonide MMX 9 mg was associated with numerically higher rates of clinical (42.2% vs 33.7%) and endoscopic improvement (42.2% vs 31.5%) versus placebo. The rate of histological healing (16.5% vs 6.7%; p=0.0361) and proportion of patients with symptom resolution (23.9% vs 11.2%; p=0.0220) were significantly higher for budesonide MMX 9 mg than placebo. Adverse event profiles were similar across groups.
Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC.
Complex researches have focused on chloride brines in the large artesian basins of the Siberian Platform. The highly concentrated ground brines are unique natural solutions that are fraught with ...unsolved mystery associated with their origin and the formation of their chemical composition. Most scientists believe that the most important process controlling the formation of these brines was interaction between palaeoseawaters and host rocks. The newest geochemical and stable isotope data (18О, 2H, 37Cl, 81Br, 87Sr/86Sr) showed that chloride sodium ground brines of the Siberian Platform originated as the result of halogenous rock leaching, whereas chloride calcium brines derive from buried bittern connate waters. The main evolutionary process was a long interaction in the water–rock system. This paper also provides information on the vast resource of multicomponent brines, so-called “liquid ores”, which are widespread over a large area of the Siberian Platform. It is an unconventional hydromineral raw material, whose use and exploitation has an extremely high potential as it may constitute a serious alternative to solid mineral deposits. The innovative methodology and pioneering methods for the processing and extraction of valuable components (especially Li) from brine are suggested.
•Extent, geochemistry and disposal of ground brines.•Different origin of sodium chloride and calcium chloride brines.•Salinity and Li content of ground brines reaching 631 g/L 566 mg/L respectively.•Innovative technology to treat multicomponent brines and produce Li concentrates.•Residual brines as source of by-products, such as Br, Mg, Ca and Na compounds.
Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).
To evaluate variation in the overall endoscopic assessment of ...severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.
A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.
There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).
The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.
The chemical composition and the isotopic characteristics of formation waters from the Siberian Platform are presented. The study involved samples of formation brines from depths ranging from 100 to ...∼4000
m at five different sites covering a large area of the Siberian Platform. Four water types were identified. The two main water types that were found are: (1) Ca–Cl brines that are believed to be the residual of an evaporated paleoseawater; and (2) Na–Cl brines that are derived mainly from halite dissolution. The origin of a third group of highly saline samples was not determined. However, the chemical and isotopic characteristics of this group of samples suggest that they were produced by various complex scenarios such as metamorphism, water–rock interaction, permafrost freezing and mixing. The last group of samples represents fresh and brackish waters across the area.
A wide range for the natural variation of Br stable isotopes (between −0.80‰ and +3.35‰) was found. The δ
81Br results obtained during this study indicate that Br stable isotopes can have large natural variations and that different evolutionary processes affecting water chemistry may cause significant fractionation.
The paper presents unique results of studying the composition of the ground ice (major components, trace elements, and rare earth elements — REEs) encountered at a depth of 200–250m in sedimentary ...and magmatic rocks in the Western Yakutia diamond-bearing regions. In addition to those established earlier, three new geochemical types of ground ice have been defined: (i) sulfate-hydrocarbonate, (ii) chloride-hydrocarbonate, and (iii) sulfate-chloride types with mixed cation composition. The ground ice geochemical features are caused by evolutionary processes of interaction in the water–rock system during permafrost formation. The enclosed rocks were the source for the addition of sulfate and chlorine ions, as well as trace elements, to the ground waters of the active water exchange zone that had existed before freezing. The distribution pattern of REEs in ground ice has a special form distinct from that of sedimentary rocks, kimberlites, and ocean waters, but similar to the REE pattern in local river waters. This REE pattern features the positive europium (Eu) anomaly and approximate equality of light and heavy REEs. The obtained results essentially expand the insight into ice-formation processes in sedimentary and magmatic rocks.
•Cement and intrusive ground ice is best developed in sedimentary and intrusive rocks.•Five geochemical types of texture-forming ground ice are distinguished.•We report unique signatures of ground ice, including trace elements and REEs.•The REE profile for ground ice features a Ʌ-shaped pattern with positive Eu anomaly.
Research has been conducted on the permafrost in the Sentsa River valley for the first time. The investigated units of the permafrost are cryogenic structures of unconsolidated deposits and active ...layer temperature, morphology and cross-section of sizable frost mounds and chemical composition of ice core. The complex pilot studies included borehole drilling, detailed documentation of frost borehole samples, penetrated sections of frost mounds, and river terrace cusps, tachometric survey of the Sentsa river valley, GPS-anchoring of reference sections and boreholes, defining the ice content (humidity), and the lithological, grain-size and microaggregate composition of lacustrine-alluvial sediments. The analysis has been performed by the specialists of the Center for Geodynamics and Geochronology located at the Institute of the Earth's Crust, Irkutsk using modern methods. According to the preliminary data, frost mounds are cryogenic formations of mixed segregation-intrusive genesis. The permafrost thermal regime observations have shown that significant temperature variations occur in the layer 0-2 m, and below the rock temperature is negative in the two-year cycle. It varies from -1.6 °C (in winter) to -0.8 °C (in summer) at depth 4.4 m. The rock temperature is constant (-2.1°C) at depth 10 m.
The ice-rich core formation within the core of the lithalsa in the Sentsa River valley (West Buryatia) was studied. The concentrations of stable oxygen and hydrogen isotopes in the ice were ...determined, the plant residues in the enclosing deposits were aged. It was found that the lacustrine loams enclosing the ice body were accumulated about 4700–7000 years ago. The ice core of the lithalsa was characterized by δD values from 141.9 to–159.8‰, δ
18
O from–19.52 to–21‰, and
d
exc
within 4.1–17.29‰. Small variations in the isotope composition of the ice–soil material within the lithalsa core point to its formation in an open system with water inflow from outside. The values of δ
18
O and δD were much closer to those for recent middle-winter and late-autumn atmospheric precipitation, as well as for riverine water, which pointed to a Holocene age of the ice.
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