| 1. |
- Andersson, Maria L., et al.
(författare)
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Distribution of erosions in hands and feet at the time for the diagnosis of RA and during 8-year follow-up
- 2021
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 40:5, s. 1799-1810
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Tidskriftsartikel (refereegranskat)abstract
- Background: Joint destruction in rheumatoid arthritis (RA) is usually evaluated by radiographs of both hands and feet, while the inflammatory status mostly is evaluated by DAS28 which, however, does not include the feet. Objectives: To investigate the distribution of erosions in hands and feet in early RA over 8 years and its potential clinical implications. Furthermore, the group of patients never showing erosions has been addressed. Methods: This study comprises 1041 patients from the BARFOT study of patients with early RA. Radiographs of hands and feet were performed at baseline, 1, 2, 5, and 8 years and evaluated by the Sharp van der Heijde scoring (SHS) method (32 joints in the hands and 12 in the feet). Disease activity was measured by DAS28, SR, CRP, and function with HAQ. Results: In the feet, there were significantly more eroded joints in percent of examined joints than in the hands at all time points. Patients with erosions only in the feet were younger, more often seropositive and smokers. They had significantly lower baseline DAS28, than the patients with erosions only in the hands. The patients without erosions over time were, at diagnosis, significantly younger and less frequently seropositive compared with patients having erosions. Conclusions: This study highlights the importance of evaluating the feet in patients with RA, both with clinical examinations and with imaging and lends support to the notion that seropositivity and smoking are risk factors for erosive disease. Further studies of patients with nonerosive disease are needed.Key Points:• Foot problems are common in RA• This study emphasizes the limitations of DAS28 and Sharp van der Heijde score as regards evaluating disease activity and radiographic damage• This study highlights the importance of evaluating the feet in patients with RA with clinical examinations and imaging• This study also points out the need of further studies of patients with non-erosive RA.
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| 2. |
- de Rooy, D. P. C., et al.
(författare)
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Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:7, s. 1384-1387
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Tidskriftsartikel (refereegranskat)abstract
- Background Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. Objective To determine the effect of smoking on joint damage progression. Methods Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. Results When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). Conclusions This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.
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| 3. |
- Eberhardt, K., et al.
(författare)
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THU0104 Physical Function in Relation to Gender in Patients with Rheumatoid Arthritis – A 15 Year Follow up Study from the Barfot Cohort
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 74, s. 230-231
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim was to study physical function in individuals with rheumatoid arthritis (RA) as measured by SOFI (observed physical function) and HAQ (self-rated physical function) over 15 years and describe associated variables, with focus on gender differences.Methods In all 2558 patients (847 men and 1711 women) age (SD) 58 (16) were recruited from the BARFOT inception cohort of patients with early RA. They had at inclusion a disease duration of one year or less and fulfilled the ACR 1987 criteria. At 15 years follow-up 663 out of 690 patients participated. Physical function was assessed by the SOFI (Signals of functional impairment) test, (scores 0-44, best to worst) which includes 12 performance tests measuring objective physical function, and the HAQ (Health Assessment Questionnaire) (scores 0-3, best to worst) measuring self-reported activity. A logistic regression model was performed to assess if being in the highest quartile of SOFI and HAQ, respectively, at the15 year follow up visit was associated to gender. Age, disease duration at inclusion, disease activity, smoking habits, RF positivity and pain were included in the model.Results Women had lower mean SOFI than men at inclusion and during the first study year, p<0.001. HAQ showed a conversed pattern, where women reported worse physical function than men on all occasions, p<0.001. During the first year SOFI and HAQ decreased in both genders, p<0.001. Thereafter throughout the study period mean SOFI and HAQ increased in men and women, p<0.001, figure 1A and B.At the 15 year follow up visit being in the highest quartile of SOFI (score ≥10) was not associated with gender while women had a higher risk to be in the highest quartile of HAQ (score ≥1.13) OR (95% CI) 2.86 (1.73-4.74), p<0.001. DAS 28 at inclusion showed a weak association with SOFI, OR (95% CI) 1.36 (1.11-1.68), p=0.003 while pain at inclusion was somewhat closer associated with HAQ, 1.02 (1.01-1.03), p<0.001. The correlation between the two functional test was r=0.54.Conclusions Women had an almost three times higher risk of worse outcome of HAQ after 15 years while the outcome of SOFI was not associated with gender. These two measures provide information of different aspects of physical function and should be used concomitantly.Disclosure of Interest None declared
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| 4. |
- Mukonzo, Jackson K, et al.
(författare)
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A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.
- 2009
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Ingår i: British journal of clinical pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 68:5, s. 690-9
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM. METHODS: Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. RESULTS: Apparent oral clearance (95% confidence interval) was 4 l h l(-1) (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The apparent peripheral volume of distribution was twofold higher in women compared with men. CONCLUSIONS: The model identified the four factors CYP2B6*6, CYP2B6*11, a novel variant allele in ABCB1 (rs3842) and sex as major predictors of efavirenz plasma exposure in a healthy Ugandan population after single-dose administration. Use of mixed-effects modelling allowed the analysis and integration of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model.
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