Background:
Life participation is an outcome of critical importance to patients receiving peritoneal dialysis (PD). However, there is no widely accepted or validated tool for measuring life ...participation in patients receiving PD.
Methods:
Online consensus workshop to identify the essential characteristics of life participation as a core outcome, with the goal of establishing a patient-reported outcome measure for use in all trials in patients receiving PD. Thematic analysis of transcripts was performed.
Results:
Fifty-six participants, including 17 patients and caregivers, from 15 countries convened via online videoconference. Four themes were identified: reconfiguring expectations of daily living (accepting day-to-day fluctuation as the norm, shifting thresholds of acceptability, preserving gains in flexibility and freedom), ensuring broad applicability and interpretability (establishing cross-cultural relevance, incorporating valued activities, distinguishing unmodifiable barriers to life participation), capturing transitions between modalities and how they affect life participation (responsive to trajectory towards stable, reflecting changes with dialysis transitions) and maximising feasibility of implementation (reducing completion burden, administrable with ease and flexibility).
Conclusions:
There is a need for a validated, generalisable outcome measure for life participation in patients receiving PD. Feasibility, including length of time to complete and flexible mode of delivery, are important to allow implementation in all trials that include patients receiving PD.
Graphical Abstract
This is a visual representation of the abstract.
The aorta is a major source of cerebral thromboembolism, but its role in stroke pathogenesis is not well understood due to its poor accessibility for non-invasive imaging. We examined whether ...thoracic aortic calcification (TAC), a marker of aortic plaque load, is associated with stroke in addition to established risk factors.
A total of 3930 subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for incident stroke events over 109.0 ± 23.3 months. Cox proportional hazards regressions were used to examine associations with stroke of TAC in addition to established risk factors (age, sex, systolic blood pressure, LDL, HDL, diabetes, and smoking) and coronary artery calcification (CAC). 101 incident strokes occurred during the follow-up period. Subjects suffering a stroke had significantly higher TAC values at baseline than the remaining subjects (median = 83.1 Q1;Q3 = 4.7;472.9 vs. 15.7 0.0;117.1; P < 0.001). In a multivariable Cox proportional hazards regression, log(TAC + 1) (hazards ratio HR = 1.09 95% confidence interval = 1.00-1.19; P = 0.044) was associated with stroke in addition to established risk factors. Further analyses revealed that log(DTAC + 1), i.e. calcification of the descending aorta (1.11 1.02-1.20; P = 0.016), but not log(ATAC + 1), i.e. calcification of the ascending aorta (1.02 0.93-1.11; P = 0.713), was associated with stroke. The HR for log(TAC + 1) decreased to 1.06 (0.97-1.16; P = 0.202), when log(CAC + 1) was also inserted into multivariable analyses.
Calcification of the thoracic aorta, more specifically its descending segment, is associated with incident stroke in addition to established risk factors. CAC outperforms aortic calcification as a stroke predictor.
Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host ...pathogen interactions is of key interest.
In this two-center, retrospective German and Hungarian cohort study, patients with Crohn's disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed.
In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383).
IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.
A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A>G in three independent ...European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.
In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n=310; ulcerative colitis UC n=179), Hungary (CD n=147; UC n=117), and the Netherlands (CD n=157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.
We found a highly significant association of c.898A>G to CD. The association was significant (p=0.0005) for the total CD cohort but also for the individual populations from Germany (p=0.02) and Netherlands (p=0.02) whereas in the Hungarian CD patients a clear trend was observed (p=0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.
We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype.
Background: A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211) variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The aim of this study was to analyze the ...frequency of p.C10X in 3 independent European (IBD) cohorts from Germany, Hungary, and the Netherlands.
Methods: We included a European IBD cohort of 921 patients and compared the p.C10X genotype frequency to 832 healthy controls. The 3 study populations analyzed were: (1) Germany CD, n = 317; ulcerative colitis (UC), n = 180, (2) Hungary (CD, n = 149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and to clinical characteristics. Ethnically matched controls were included (German, n = 413; Hungarian, n = 202; Dutch, n = 217).
Results: We observed no significant difference in p.C10X genotype frequency in either patients with CD or patients with UC compared with controls in all 3 cohorts. Conversely to the initial association study, we found a trend toward lower frequencies of the suggestive risk wild type in CD from the Netherlands compared with controls (P = 0.14). We found neither evidence for genetic interactions between p.C10X and NOD2 nor the C10X variant to be associated with a CD or UC phenotype.
Conclusions: Analyzing 3 independent European IBD cohorts, we found no evidence that the C10X variant in CARD8 confers susceptibility for CD.
(Inflamm Bowel Dis 2007)
Recent work has suggested that important B- and T-cell epitopes on the circumsporozoite protein (CSP) of Plasmodium vivax lie external to the major repeat regions of the protein. We have studied two ...naturally exposed human populations (Caucasian and Papua New Guineans) and determined the antibody response to yeast-derived recombinant CSPs, overlapping synthetic peptides spanning amino acids 76 348 of the Belem P. vivax CSP and overlapping peptides representing the variant repeats of the VK247 strain of P. vivax. We have demonstrated that the P. vivax CSP-specific antibody response is directed towards areas within the repeat region as well as areas external to this; but the dominant epitopes recognized by the two populations studied, were distinct. One epitope, lying external to the repeats and recognized by both populations, partially overlaps an area of the protein referred to as region II-plus. Sera from malaria-exposed Papua New Guineans and Thais contained antibodies to this epitope (V22, single letter amino acid sequence TCGVGVRVRRRVNAANKKPE) which were capable of recognizing sporozoites, as determined by quantitative inhibition IFA. Seventeen percent of PNG sera had antibodies to this peptide compared with 33% who had antibodies to the central repeats of the protein. Immunization of mice with recombinant CSP did not induce antibodies to V22. However, immunization with overlapping peptide epitopes representing this region (V21 or V22) induced specific antibodies but only two sera recognized both V21 and V22 and, by inference, the overlapping peptide sequence (TCGVGVRVRR). Antibodies in these two sera could bind recombinant CSP in ELISA; however, in contrast, nine sera which recognized either V21 or V22 alone did not bind CSP. Only one of two sera containing antibodies recognizing CSP stained P. vivax sporozoites. This serum also recognized an epitope dependent upon two amino acids aminoterminal to V22. These data suggest that the fine specificity of antibodies is a critical determinant for binding to both recCSP and sporozoites.
Recent work has suggested that important B- and T-cell epitopes on the circumsporozoite protein (CSP) of
Plasmodium vivax lie external to the major repeat regions of the protein. We have studied two ...naturally exposed human populations (Caucasian and Papua New Guineans) and determined the antibody response to yeast-derived recombinant CSPs, overlapping synthetic peptides spanning amino acids 76–348 of the Belem
P. vivax CSP and overlapping peptides representing the variant repeats of the VK247 strain of
P. vivax. We have demonstrated that the
P. vivax CSP-specific antibody response is directed towards areas within the repeat region as well as areas external to this; but the dominant epitopes recognized by the two populations studied, were distinct. One epitope, lying external to the repeats and recognized by both populations, partially overlaps an area of the protein referred to as region II-plus. Sera from malaria-exposed Papua New Guineans and Thais contained antibodies to this epitope (V22, single letter amino acid sequence TCGVGVRVRRRVNAANKKPE) which were capable of recognizing sporozoites, as determined by quantitative inhibition IFA. Seventeen percent of PNG sera had antibodies to this peptide compared with 33% who had antibodies to the central repeats of the protein. Immunization of mice with recombinant CSP did not induce antibodies to V22. However, immunization with overlapping peptide epitopes representing this region (V21 or V22) induced specific antibodies but only two sera recognized both V21 and V22 and, by inference, the overlapping peptide sequence (TCGVGVRVRR). Antibodies in these two sera could bind recombinant CSP in ELISA; however, in contrast, nine sera which recognized either V21 or V22 alone did not bind CSP. Only one of two sera containing antibodies recognizing CSP stained
P. vivax sporozoites. This serum also recognized an epitope dependent upon two amino acids aminoterminal to V22. These data suggest that the fine specificity of antibodies is a critical determinant for binding to both recCSP and sporozoites.
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