Prediction model for unsuccessful return to work after hospital-based intervention in low back pain patients

BACKGROUND: Many studies on low back pain (LBP) have identified prognostic factors, but prediction models for use in secondary health care are not available. The purpose of this cohort study, based on a randomised clinical study, was to identify risk factors for unsuccessful return to work (U-RTW) in sick-listed LBP patients with or without radiculopathy and to validate a prediction model for U-RTW. METHODS: 325 sick-listed LBP patients with or without radiculopathy were included in an intervention study and followed for one year. Afterwards, 117 other LBP patients were recruited similarly, included in a validation study and also followed for one year. All patients were subjected to identical procedures and interventions and received a brief intervention by the same rehabilitation doctor and physiotherapist. Half of them received case manager guidance within a multidisciplinary setting. At baseline, they completed a questionnaire and went through a clinical low-back examination. Sciatica was investigated by magnetic resonance imaging (MRI). U-RTW was registered in a national database both initially and at 1-year. RESULTS: Neither initial U-RTW (24.0%) nor one-year U-RTW (38.2%) were statistically significantly different in the two intervention groups nor in patients with and without radiculopathy. Multivariate logistic regression analysis identified two clinical and five psychosocial baseline predictors for one-year U-RTW (primary outcome). The clinical predictors included pain score (back+leg pain) and side-flexion. The five psychosocial predictors included ‘bodily distress’ ‘low expectations of RTW’, ‘blaming the work for pain’, ‘no home ownership’ and ‘drinking alcohol less than once/month’. These predictors were not statistically significantly different in patients with and without radiculopathy, and they also predicted initial U-RTW (secondary outcome). Obesity and older age were only supplementary predictors in patients with radiculopathy. A prediction model was established and tested in the validation study group. The model predicted one-year U-RWT in patients with intermediate and high risk, but only partially in patients with low risk. The model predicted all three risk categories in initial U-RTW. CONCLUSIONS: A prediction model combining baseline clinical and psychosocial risk factors predicted patients with low, intermediate and high risk for unsuccessful return to work, both initially and at 1-year

A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case–control approach. FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology. We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment. METHODS: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. RESULTS: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥0.10). CONCLUSION: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants. TRIAL REGISTRATION: The OPERA study is registered at Clinicaltrials.gov (NCT00660647). The CIMESTRA study is not listed in a clinical trials registry, because patients were included between October 1999 and October 2002. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-014-0475-3) contains supplementary material, which is available to authorized users