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121.
122.
Loes?AM?Leenen Ben?FM?WijnenEmail author Reina?JA?de Kinderen Marian?HJM?Majoie Caroline?M?van Heugten Silvia?MAA?Evers 《BMC neurology》2014,14(1):255
Background
In patients with epilepsy, poor adherence to anti-epileptic drugs has been shown to be the most important cause of poorly controlled epilepsy. Furthermore, it has been noted that the quality of life among patients with epilepsy can be improved by counseling and treatments aimed at increasing their self-efficacy and concordance, thus stimulating self-management skills. However, there is a need for evidence on the effectiveness of such programs, especially within epilepsy care. Therefore, we have developed a multi-component intervention (MCI) which combines a self-management/education program with e-Health interventions. Accordingly, the overall objective of this study is to assess the (cost)-effectiveness and feasibility of the MCI, aiming to improve self-efficacy and concordance in patients with epilepsy.Methods
A RCT in two parallel groups will be conducted to compare the MCI with a control condition in epilepsy patients. One hundred eligible epilepsy patients will be recruited and allocated to either the intervention or control group. The intervention group will receive the MCI consisting of a self-management/education program of six meetings, including e-Health interventions, and will be followed for 12 months. The control group will receive care as usual and will be followed for 6 months, after which patients will be offered the possibility of participating in the MCI. The study will consist of three parts: 1) a clinical effectiveness study, 2) a cost-effectiveness study, and 3) process evaluation. The primary outcome will be self-efficacy. Secondary outcomes include adherence, side effects, change in seizure severity & frequency, improved quality of life, proactive coping, and societal costs. Outcome assessments will be done using questionnaires at baseline and after 3, 6, 9, and 12 months (last two applicable only for intervention group).Discussion
In times of budget constraints, MCI could be a valuable addition to the current healthcare provision for epilepsy, as it is expected that higher concordance and self-efficacy will result in reduced use of healthcare resources and an increased QOL. Accordingly, this study is aimed helping patients to be their own provider of health care, shifting epilepsy management from professionals to self-care by patients equipped with appropriate skills and tools.Trial registration number
NTR4484.123.
Nicole Willems Frances C Bach Saskia G M Plomp Mattie HP van Rijen Jeannette Wolfswinkel Guy CM Grinwis Clemens Bos Gustav J Strijkers Wouter JA Dhert Bj?rn P Meij Laura B Creemers Marianna A Tryfonidou 《Arthritis research & therapy》2015,17(1)
IntroductionStrategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain.MethodsCanine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue.ResultsIn vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7.ConclusionsAn intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users. 相似文献124.
Lone Banke Rasmussen Birgit Hollenbach Peter Laurberg Allan Carl Antonia Hg Torben Jrgensen Pernille Vejbjerg Lars Ovesen Lutz Schomburg 《Journal of trace elements in medicine and biology》2009,23(4):265-271
Selenium is an essential micronutrient important to human health. The main objective of this study is to describe serum selenium and selenoprotein P status in two samples of the Danish population. In addition, the influence of various factors potentially associated with selenium status was investigated.Blood samples from a total of 817 randomly selected subjects from two cities in Denmark were analyzed. Half of the samples were collected in 1997–1998 and the other half in 2004–2005. Samples from women aged 18–22, 40–45 and 60–65 years, and men aged 60–65 years were selected for this study. All subjects had filled in a food frequency questionnaire (FFQ) and a questionnaire with information about smoking habits, alcohol consumption and exercise habits.Mean serum selenium level was 98.7±19.8 μg/L and median selenoprotein P level was 2.72 (2.18–3.49) mg/L. Serum selenium and selenoprotein P increased with age, and selenoprotein P was higher in men than in women. Serum selenium levels decreased by 5% on average from 1997–98 to 2004–05 (P<0.001), whereas selenoprotein P level increased (P<0.001). The intake of fish correlated weakly with serum selenium level (r=0.14, P<0.001) but not with selenoprotein P level. Smoking status, alcohol intake, exercise habits, BMI and medicine use did not influence selenium status.It is concluded that selenium status in this Danish population is at an acceptable level. No major groups with regard to age, sex or lifestyle factors could be identified as being in risk for selenium deficiency. 相似文献
125.
Cynthia Vierra-Green David Roe Lihua Hou Carolyn Katovich Hurley Raja Rajalingam Elaine Reed Tatiana Lebedeva Neng Yu Mary Stewart Harriet Noreen Jill A. Hollenbach Lisbeth A. Guethlein Tao Wang Stephen Spellman Martin Maiers 《PloS one》2012,7(11)
The immune responses of natural killer cells are regulated, in part, by killer cell immunoglobulin-like receptors (KIR). The 16 closely-related genes in the KIR gene system have been diversified by gene duplication and unequal crossing over, thereby generating haplotypes with variation in gene copy number. Allelic variation also contributes to diversity within the complex. In this study, we estimated allele-level haplotype frequencies and pairwise linkage disequilibrium statistics for 14 KIR loci. The typing utilized multiple methodologies by four laboratories to provide at least 2x coverage for each allele. The computational methods generated maximum-likelihood estimates of allele-level haplotypes. Our results indicate the most extensive allele diversity was observed for the KIR framework genes and for the genes localized to the telomeric region of the KIR A haplotype. Particular alleles of the stimulatory loci appear to be nearly fixed on specific, common haplotypes while many of the less frequent alleles of the inhibitory loci appeared on multiple haplotypes, some with common haplotype structures. Haplotype structures cA01 and/or tA01 predominate in this cohort, as has been observed in most populations worldwide. Linkage disequilibrium is high within the centromeric and telomeric haplotype regions but not between them and is particularly strong between centromeric gene pairs KIR2DL5∼KIR2DS3S5 and KIR2DS3S5∼KIR2DL1, and telomeric KIR3DL1∼KIR2DS4. Although 93% of the individuals have unique pairs of full-length allelic haplotypes, large genomic blocks sharing specific sets of alleles are seen in the most frequent haplotypes. These high-resolution, high-quality haplotypes extend our basic knowledge of the KIR gene system and may be used to support clinical studies beyond single gene analysis. 相似文献
126.
127.
Huang W Naughton MA Yang H Su T Dam S Wong PW Arfsten A Edwards S Sinha U Hollenbach S Scarborough RM Zhu BY 《Bioorganic & medicinal chemistry letters》2003,13(4):723-728
A series of novel transition state factor Xa inhibitors containing a variety of lactam ring systems as central templates was synthesized in an expedient manner and allowed for a great deal of structural variability. Among them, the piperazinone-based inhibitors were found to be not only active against factor Xa but also selective over thrombin. Optimization of the P4 moiety yielded several potent compounds with IC(50) below 1 nM against factor Xa. 相似文献
128.
Price DJ Campbell PG Sutton AG Grech ED Davies A Hall JA De Belder MA 《International journal of cardiovascular interventions》2001,4(1):15-20
BACKGROUND: The EPISTENT trial reported improved early outcomes with routine use of abciximab after coronary stenting. Increasing use of stents means that routine abciximab adds significantly to costs of percutaneous coronary intervention (PCI). This paper reports the results of a protocol encouraging restriction of abciximab therapy to high-risk patients only. METHODS: Data were collected prospectively over a 34-month period for patients undergoing PCI with stenting. In addition to those who fulfilled criteria for inclusion in the EPISTENT trial, patients treated in the setting of acute myocardial infarction (AMI) were studied. Demographic data, procedural details and early clinical outcomes were recorded. RESULTS: Of 808 patients studied, 601 fulfilled EPISTENT inclusion criteria and comprised 367 patients (45%) treated for stable angina and 234 (30%) treated for unstable or post-infarct angina. The additional 207 patients (25%) were treated during AMI. The 808 patients received a total of 981 stents. Abciximab was given in only 88 cases (10.9%). Major adverse clinical events occurred in 39 patients (4.8%). CONCLUSION: Selective use of abciximab for patients undergoing coronary stenting can be associated with outcomes equivalent to those reported for routine use, but with significant cost savings. 相似文献
129.
Thiamin (Vitamin B(1)) transport in Escherichia coli occurs by the superfamily of traffic ATPases in which the initial receptor is the periplasmic binding protein. We have cloned the periplasmic thiamin-binding protein (TBP) of the E. coli periplasmic thiamin transport system and purified the overexpressed protein to apparent homogeneity. A subsequent biochemical characterization demonstrates that TBP is a 34.205kDa monomer. TBP also contains one tightly bound thiamin species [thiamin, thiamin monophosphate (TMP), or thiamin diphosphate (TDP)] per monomer (K(D)=0.8 microM) when isolated under conditions that would remove any loosely bound ligands. We also demonstrate that thiamin is readily exchangeable in the presence of exogenous thiamin with a k(off)=0.12s(-1). The biochemical characteristics of the overexpressed, plasmid-derived TBP are indistinguishable from those determined for endogenous TBP purified from E. coli. The overexpression and purification of TBP that we present here allows the rapid isolation of large amounts of pure protein that are required for further mechanistic and structural studies and demonstrates a vast improvement over previously reported purifications. 相似文献
130.
A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony 总被引:24,自引:1,他引:23
The method of evolutionary parsimony--or operator invariants--is a
technique of nucleic acid sequence analysis related to parsimony analysis
and explicitly designed for determining evolutionary relationships among
four distantly related taxa. The method is independent of substitution
rates because it is derived from consideration of the group properties of
substitution operators rather than from an analysis of the probabilities of
substitution in branches of a tree. In both parsimony and evolutionary
parsimony, three patterns of nucleotide substitution are associated
one-to-one with the three topologically linked trees for four taxa. In
evolutionary parsimony, the three quantities are operator invariants. These
invariants are the remnants of substitutions that have occurred in the
interior branch of the tree and are analogous to the substitutions assigned
to the central branch by parsimony. The two invariants associated with the
incorrect trees must equal zero (statistically), whereas only the correct
tree can have a nonzero invariant. The chi 2-test is used to ascertain the
nonzero invariant and the statistically favored tree. Examples, obtained
using data calculated with evolutionary rates and branchings designed to
camouflage the true tree, show that the method accurately predicts the
tree, even when substitution rates differ greatly in neighboring peripheral
branches (conditions under which parsimony will consistently fail). As the
number of substitutions in peripheral branches becomes fewer, the parsimony
and the evolutionary-parsimony solutions converge. The method is robust and
easy to use.
相似文献