Modern psychometrics applied in rheumatology - a systematic review

Background Although item response theory (IRT) appears to be increasingly used within health care research in general, a comprehensive overview of the frequency and characteristics of IRT analyses within the rheumatic field is lacking. An overview of the use and application of IRT in rheumatology to date may give insight into future research directions and highlight new possibilities for the improvement of outcome assessment in rheumatic conditions. Therefore, this study systematically reviewed the application of IRT to patient-reported and clinical outcome measures in rheumatology. Methods Literature searches in PubMed, Scopus and Web of Science resulted in 99 original English-language articles which used some form of IRT-based analysis of patient-reported or clinical outcome data in patients with a rheumatic condition. Both general study information and IRT-specific information were assessed. Results Most studies used Rasch modeling for developing or evaluating new or existing patient-reported outcomes in rheumatoid arthritis or osteoarthritis patients. Outcomes of principle interest were physical functioning and quality of life. Since the last decade, IRT has also been applied to clinical measures more frequently. IRT was mostly used for evaluating model fit, unidimensionality and differential item functioning, the distribution of items and persons along the underlying scale, and reliability. Less frequently used IRT applications were the evaluation of local independence, the threshold ordering of items, and the measurement precision along the scale. Conclusion IRT applications have markedly increased within rheumatology over the past decades. To date, IRT has primarily been applied to patient-reported outcomes, however, applications to clinical measures are gaining interest. Useful IRT applications not yet widely used within rheumatology include the cross-calibration of instrument scores and the development of computerized adaptive tests which may reduce the measurement burden for both the patient and the clinician. Also, the measurement precision of outcome measures along the scale was only evaluated occasionally. Performed IRT analyses should be adequately explained, justified, and reported. A global consensus about uniform guidelines should be reached concerning the minimum number of assumptions which should be met and best ways of testing these assumptions, in order to stimulate the quality appraisal of performed IRT analyses

Elevated CO2 emissions during magmatic-hydrothermal degassing at Awu Volcano, Sangihe Arc, Indonesia

Awu is a remote and little known active volcano of Indonesia located in the northern part of Molucca Sea. It is the northernmost active volcano of the Sangihe arc with 18 eruptions in less than 4 centuries, causing a cumulative death toll of 11,048. Two of these eruptions were classified with a Volcanic Explosivity Index (VEI) of 4. Since 2004, a lava dome has occupied the centre of Awu crater, channelling the fumarolic gas output along the crater wall. A combined Differential Optical Absorption Spectroscopy (DOAS) and Multi-component Gas Analyzer System (Multi-GAS) study highlight a relatively small SO2 flux (13 t/d) sustained by mixed magmatic–hydrothermal emissions made-up of 82 mol.% H2O, 15 mol.% CO2, 2.55 mol.% total S (ST) and 0.02 mol.% H2. The CO2 emission budget, as observed during a short observation period in 2015, corresponds to a daily contribution to the atmosphere of 2600 t/d, representing 1% of the global CO2 emission budget from volcanoes. The gas CO2/ST ratio of 3.7 to 7.9 is at the upper limit of the Indonesian gas range, which is ascribed to (i) some extent of S loss during hydrothermal processing, and perhaps (ii) a C-rich signature of the feeding magmatic gas phase. The source of this high CO2 signature and flux is yet to be fully understood; however, given the peculiar geodynamic context of the region, dominated by the arc-to-arc collision, this may result from either the prolonged heating of the slab and consequent production of carbon-rich fluids, or the recycling of crustal carbon

Reduced basis isogeometric mortar approximations for eigenvalue problems in vibroacoustics

We simulate the vibration of a violin bridge in a multi-query context using reduced basis techniques. The mathematical model is based on an eigenvalue problem for the orthotropic linear elasticity equation. In addition to the nine material parameters, a geometrical thickness parameter is considered. This parameter enters as a 10th material parameter into the system by a mapping onto a parameter independent reference domain. The detailed simulation is carried out by isogeometric mortar methods. Weakly coupled patch-wise tensorial structured isogeometric elements are of special interest for complex geometries with piecewise smooth but curvilinear boundaries. To obtain locality in the detailed system, we use the saddle point approach and do not apply static condensation techniques. However within the reduced basis context, it is natural to eliminate the Lagrange multiplier and formulate a reduced eigenvalue problem for a symmetric positive definite matrix. The selection of the snapshots is controlled by a multi-query greedy strategy taking into account an error indicator allowing for multiple eigenvalues

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Local structure study of In_xGa_(1-x)As semiconductor alloys using High Energy Synchrotron X-ray Diffraction

Nearest and higher neighbor distances as well as bond length distributions (static and thermal) of the In_xGa_(1-x)As (0<x<1) semiconductor alloys have been obtained from high real-space resolution atomic pair distribution functions (PDFs). Using this structural information, we modeled the local atomic displacements in In_xGa_(1-x)As alloys. From a supercell model based on the Kirkwood potential, we obtained 3-D As and (In,Ga) ensemble averaged probability distributions. This clearly shows that As atom displacements are highly directional and can be represented as a combination of and displacements. Examination of the Kirkwood model indicates that the standard deviation (sigma) of the static disorder on the (In,Ga) sublattice is around 60% of the value on the As sublattice and the (In,Ga) atomic displacements are much more isotropic than those on the As sublattice. The single crystal diffuse scattering calculated from the Kirkwood model shows that atomic displacements are most strongly correlated along directions.Comment: 10 pages, 12 figure

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Analysis of IL12B Gene Variants in Inflammatory Bowel Disease

IL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, the phenotypic effects and potential gene-gene interactions of IL12B variants are largely unknow

Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence:A population-based cohort study

Introduction: When risk estimation in older patients with hormone receptor positive breast cancer (HR + BC) is based on the same factors as in younger patients, age-related factors regarding recurrence risk and other-cause mortality are not considered. Genomic risk assessment could help identify patients with ultralow risk BC who can forgo adjuvant treatment. However, assessment tools should be validated specifically for older patients. This study aims to determine whether the 70-gene signature test (MammaPrint) can identify patients with HR + BC aged ≥70 years with ultralow risk for distant recurrence. Materials and Methods: Inclusion criteria: ≥70 years; invasive HR + BC; T1-2N0-3M0. Exclusion criteria: HER2 + BC; neoadjuvant therapy. MammaPrint assays were performed following standardized protocols. Clinical risk was determined with St. Gallen risk classification. Primary endpoint was 10-year cumulative incidence rate of distant recurrence in relation to genomic risk. Subdistribution hazard ratios (sHR) were estimated from Fine and Gray analyses. Multivariate analyses were adjusted for adjuvant endocrine therapy and clinical risk. Results: This study included 418 patients, median age 78 years (interquartile range [IQR] 73–83). Sixty percent of patients were treated with endocrine therapy. MammaPrint classified 50 patients as MammaPrint-ultralow, 224 patients as MammaPrint-low, and 144 patients as MammaPrint-high risk. Regarding clinical risk, 50 patients were classified low, 237 intermediate, and 131 high. Discordance was observed between clinical and genomic risk in 14 MammaPrint-ultralow risk patients who were high clinical risk, and 84 patients who were MammaPrint-high risk, but low or intermediate clinical risk. Median follow-up was 9.2 years (IQR 7.9–10.5). The 10-year distant recurrence rate was 17% (95% confidence interval [CI] 11–23) in MammaPrint-high risk patients, 8% (4–12) in MammaPrint-low (HR 0.46; 95%CI 0.25–0.84), and 2% (0–6) in MammaPrint-ultralow risk patients (HR 0.11; 95%CI 0.02–0.81). After adjustment for clinical risk and endocrine therapy, MammaPrint-high risk patients still had significantly higher 10-year distant recurrence rate than MammaPrint-low (sHR 0.49; 95%CI 0.26–0.90) and MammaPrint-ultralow patients (sHR 0.12; 95%CI 0.02–0.85). Of the 14 MammaPrint-ultralow, high clinical risk patients none developed a distant recurrence. Discussion: These data add to the evidence validating MammaPrint's ultralow risk threshold. Even in high clinical risk patients, MammaPrint-ultralow risk patients remained recurrence-free ten years after diagnosis. These findings justify future studies into using MammaPrint to individualize adjuvant treatment in older patients

Towards an optimal therapy strategy for myogenous TMD, physiotherapy compared with occlusal splint therapy in an RCT with therapy-and-patient-specific treatment durations

Appendix. Threshold of signs and symptoms. Post-hoc power analysis on measures of effectiveness. Two-way ANOVA statistical analysis for pain intensity. Rules for progressing and ending splint therapy. Rules for progressing and ending physiotherapy. A stepped-care model including two possible therapies. (PDF 86 kb

Breast cancer mortality of older patients with and without recurrence analysed by novel multi-state models

Introduction: In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregio-nal or distant recurrence in a population-based cohort of older patients analysed by multi-state models. Methods: Surgically treated patients >70 years diagnosed with stage I-III breast cancer in 2003-2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. Results: Overall, 18,419 patients were included. Ten-year cumulative incidences of locoregio-nal and distant recurrence were 2.8% (95%CI 2.6-3.1%) and 12.5% (95%CI 11.9-13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7-24.2%) in patients 70-74 years to 73.8% (95%CI 72.2-75.4%) in those >80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4-1.3% and 10.2-14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2-96.4%), 93.1% (95%CI 91.6-94.6%), and 88.6% (95%CI 86.5-90.8%) in patients 70-74, 75-79, and >80 years. Conclusion: In older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Experimentele farmacotherapi