124 research outputs found
Effectiveness and safety of vedolizumab induction with or without budesonide in patients with moderately to severely active Crohn's disease in Europe: a retrospective observational study
BACKGROUND
Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn's disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland.
METHODS
This retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups.
RESULTS
Overall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0-98.0] and 95 [70.0-98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%).
CONCLUSIONS
In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD.
TRIAL REGISTRATION
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Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma
<p>Abstract</p> <p>Background</p> <p>Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo.</p> <p>Methods</p> <p>In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined.</p> <p>Results</p> <p>Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues.</p> <p>Conclusion</p> <p>The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.</p
Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment
Background and purpose An internet-based discrete choice
experiment (DCE) was conducted to elicit preferences for a wide
range of Dupuytren’s contracture (DC)-related health states. An
algorithm was subsequently developed to convert these preferences
into health state utilities that can be used to assess DC’s
impact on quality of life and the value of its treatments.
Methods Health state preferences for varying levels of DC
hand severity were elicited via an internet survey from a sample
of the UK adult population. Severity levels were deined using a
combination of contractures (0, 45, or 90 degrees) in 8 proximal
interphalangeal and metacarpophalangeal joints of the index,
middle, ring, and little ingers. Right-handed, left-handed, and
ambidextrous respondents indicated which hand was preferable
in each of the 10 randomly-selected hand-pairings comparing
different DC severity levels. For consistency across comparisons,
anatomically precise digital hand drawings were used. To anchor
preferences onto the traditional 0–1 utility scale used in health
economic evaluations, unaffected hands were assigned a utility
of 1.0 whereas the utility for a maximally affected hand (i.e., all
8 joints set at 90 degrees of contracture) was derived by asking
respondents to indicate what combination of attributes and levels
of the EQ-5D-5L proile most accurately relects the impact of
living with such hand. Conditional logistic models were used to
estimate indirect utilities, then rescaled to the anchor points on
the EQ-5D-5L.
Results Estimated utilities based on the responses of 1,745
qualiied respondents were 0.49, 0.57, and 0.63 for completely
affected dominant hands, non-dominant hands, or ambidextrous
hands, respectively. Utility for a dominant hand with 90-degree
contracture in t h e metacarpophalangeal joints of the ring and
little ingers was estimated to be 0.89. Separately, reducing the
contracture of metacarpophalangeal joint for a little inger from
50 to 12 degrees would improve utility by 0.02.
Interpretation DC is associated with substantial utility decrements.
The algorithms presented herein provide a robust and lexible
framework to assess utility for varying degrees of DC severity
Conceptual Graphs Based Information Retrieval in HealthAgents
This paper focuses on the problem of representing, in a meaningful way, the knowledge involved in the HealthAgents project. Our work is motivated by the complexity of representing Electronic Health-care Records in a consistent manner. We present HADOM (HealthAgents Domain Ontology) which conceptualises the required HealthAgents information and propose describing the sources knowledge by the means of Conceptual Graphs (CGs). This allows to build upon the existing ontology permitting for modularity and °exibility. The novelty of our approach lies in the ease with which CGs can be placed above other formalisms and their potential for optimised querying and retrieval
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Novel European free-living, non-diazotrophic Bradyrhizobium isolates from contrasting soils that lack nodulation and nitrogen fixation genes - a genome comparison
The slow-growing genus Bradyrhizobium is biologically important in soils, with different representatives
found to perform a range of biochemical functions including photosynthesis, induction of root nodules
and symbiotic nitrogen fixation and denitrification. Consequently, the role of the genus in soil ecology
and biogeochemical transformations is of agricultural and environmental significance. Some isolates of
Bradyrhizobium have been shown to be non-symbiotic and do not possess the ability to form nodules.
Here we present the genome and gene annotations of two such free-living Bradyrhizobium isolates,
named G22 and BF49, from soils with differing long-term management regimes (grassland and bare
fallow respectively) in addition to carbon metabolism analysis. These Bradyrhizobium isolates are
the first to be isolated and sequenced from European soil and are the first free-living Bradyrhizobium
isolates, lacking both nodulation and nitrogen fixation genes, to have their genomes sequenced and
assembled from cultured samples. The G22 and BF49 genomes are distinctly different with respect
to size and number of genes; the grassland isolate also contains a plasmid. There are also a number
of functional differences between these isolates and other published genomes, suggesting that this
ubiquitous genus is extremely heterogeneous and has roles within the community not including
symbiotic nitrogen fixation
Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study
Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation.
Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units.
Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4–11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0–64.9) when LOH was 11–15 days, and by 72.0% (95%CI = 42.6–107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4–36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk.
Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments
DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia
Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia
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