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1.
Arthritis Res Ther ; 25(1): 131, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37501212

ABSTRACT

INTRODUCTION: Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI) ≥ 33 kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight). METHODS: VLED (640 kcal/day) during 12 or 16 weeks, depending on BL BMI < 40 or ≥ 40 kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6. RESULTS: Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p < 0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p < 0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS = 0.671, p < 0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin. CONCLUSIONS: Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.


Subject(s)
Arthritis, Psoriatic , Leptin , Humans , Adiponectin , Interleukin-23 , Obesity/complications , Obesity/therapy , Adipokines , Cytokines , Weight Loss , Tumor Necrosis Factor-alpha
2.
Osteoporos Int ; 33(1): 205-216, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34263348

ABSTRACT

Patients with ankylosing spondylitis (AS) have impaired volumetric bone mineral density (vBMD) assessed with high-resolution peripheral computed tomography (HRpQCT). This first longitudinal HRpQCT study in AS shows that cortical and trabecular vBMD decreased at tibia and that signs of inflammation were associated with cortical bone loss at tibia and radius. INTRODUCTION: Patients with ankylosing spondylitis (AS) have reduced volumetric bone mineral density (vBMD) in the peripheral skeleton assessed with high-resolution peripheral quantitative computed tomography (HRpQCT). The aims were to investigate longitudinal changes in vBMD, cortical area, and microarchitecture and to assess factors associated with changes in vBMD and cortical area in men with AS. METHODS: HRpQCT of radius and tibia was performed in 54 men with AS at baseline and after 5 years. Univariate and multivariable linear regression analyses were used. RESULTS: At tibia, there were significant decreases exceeding least significant changes (LSC) in cortical and trabecular vBMD, mean (SD) percent change -1.0 (1.9) and -2.7 (5.0) respectively (p<0.001). In multivariable regression analyses, increase in disease activity measured by ASDAS_CRP from baseline to follow-up was associated with decreases in cortical vBMD (ß -0.86, 95% CI -1.31 to -0.41) and cortical area (ß -1.66, 95% CI -3.21 to -0.10) at tibia. At radius, no changes exceeded LSC. Nonetheless, increase in ASDAS_CRP was associated with decreases in cortical vBMD, and high time-averaged ESR was associated with decreases in cortical area. Treatment with TNF inhibitor ≥ 4 years during follow-up was associated with increases in cortical vBMD and cortical area at tibia, whereas exposure to bisphosphonates was associated with increases in cortical measurements at radius. No disease-related variables or treatments were associated with changes in trabecular vBMD. CONCLUSION: The findings in this first longitudinal HRpQCT study in patients with AS strengthen the importance of controlling disease activity to maintain bone density in the peripheral skeleton.


Subject(s)
Bone Density , Spondylitis, Ankylosing , Absorptiometry, Photon , Cortical Bone , Humans , Male , Prospective Studies , Radius/diagnostic imaging , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/drug therapy , Tibia/diagnostic imaging
4.
Arthritis Res Ther ; 19(1): 173, 2017 07 24.
Article in English | MEDLINE | ID: mdl-28738835

ABSTRACT

BACKGROUND: Nephrolithiasis (NL) is known to be associated with gout, although there are few comparative studies on risk and risk factors for NL in gout compared to population cohorts. In this cohort study we investigated: (1) overall incidence of NL in gout (cases) and general population controls; (2) risk and risk factors (common comorbidities and medications) for first-time NL in cases and controls separately. METHODS: Cases (n = 29,968) and age-matched and sex-matched controls (n = 138,678) were identified from the regional healthcare database in western Sweden (VEGA). The analyzed risk factors (comorbidities and current medication use) for first-time NL, and socioeconomic factors were retrieved from VEGA and other national Swedish registers. For cases, follow up began on 1 January 2006 or on the first diagnosis of gout if this occurred later, and for controls on their index patient's first diagnosis of gout. Follow up ended on death, emigration or 31 December 2012. Incidence rates (IR) per 1000 person-years and hazard ratios (HR) were calculated. The incidence calculations were performed for cases (regardless of prior NL) and their controls. HRs with first occurrence of NL as outcome were calculated only in those without previous NL. RESULTS: In cases there were 678 NL events (IR: 6.16 events per 1000 person-years (95% CI: 5.70-6.64) and in controls 2125 NL events (IR 3.85 events per 1000 person-years (95% CI: 3.69-4.02), resulting in an age-sex-adjusted incidence rate ratio of 1.60 (95% CI:1.47-1.74). Point estimates for predictive factors were similar in cases and controls, except for a significant interaction for losartan which increased the risk of NL only in controls (HR = 1.49 (95% CI: 1.03-2.14). Loop diuretics significantly decreased the risk of NL by 30-34% in both cases and controls. Further significant predictors of NL in gout cases were male sex, diabetes and obesity and in controls male sex and kidney disease. CONCLUSIONS: The risk (age and sex adjusted) of NL was increased by 60% in cases compared to controls. None of the commonly used medications increased the risk of NL in gout patients.


Subject(s)
Gout/epidemiology , Nephrolithiasis/epidemiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Young Adult
5.
Ann Rheum Dis ; 76(7): 1245-1252, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28073801

ABSTRACT

OBJECTIVES: To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. METHODS: Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. RESULTS: During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration <5 years and 14% for disease duration ≥5 years (adjusted HR 2.1 (95% CI 1.4 to 3.2)). For patients with full work ability at bio-start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. CONCLUSIONS: A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Registries , Return to Work/statistics & numerical data , Sick Leave/statistics & numerical data , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Arthritis, Rheumatoid/physiopathology , Female , Humans , Male , Middle Aged , Pensions , Proportional Hazards Models , Sweden , Young Adult
6.
Ann Rheum Dis ; 76(1): 17-28, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27697765

ABSTRACT

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.


Subject(s)
Cardiovascular Diseases/prevention & control , Physician's Role , Rheumatology , Risk Management , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/drug therapy , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Cardiovascular Diseases/etiology , Directive Counseling , Humans , Life Style , Risk Assessment , Risk Factors , Risk Management/methods , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/drug therapy
7.
Brain Inj ; 30(8): 969-74, 2016.
Article in English | MEDLINE | ID: mdl-27185082

ABSTRACT

PRIMARY OBJECTIVE: To describe vocational outcome 6-15 years after a traumatic brain injury (TBI) among individuals who were productive by working or studying at the time of their TBI and determine the associations with variables related to the time of injury and at follow-up. METHODS AND PROCEDURES: Thirty-four individuals with a mild TBI and 45 with a moderate-to-severe TBI were assessed on average 10 years post-injury. Logistic regression was used to determine the association between their current vocational situation and variables related to the time of injury (gender, age, injury severity and educational level) and at follow-up (time since injury, marital status and overall disability). RESULTS: A total of 67% were productive at follow-up. Age at injury, injury severity and the degree of disability at follow-up were strongly associated with being productive. Younger individuals with milder TBI and less severe disability were significantly more likely to be fully productive. No significant associations were found between productivity and gender, education, time since injury or marital status. CONCLUSIONS: This study indicates that return to productivity in a long-term perspective after a TBI is possible, in particular when the individual is young, has sustained a mild TBI and has a milder form of overall disability.


Subject(s)
Brain Injuries, Traumatic/rehabilitation , Disabled Persons , Employment , Rehabilitation, Vocational , Adolescent , Adult , Aged , Disability Evaluation , Educational Status , Female , Follow-Up Studies , Humans , Injury Severity Score , Male , Middle Aged , Young Adult
8.
Oncogene ; 35(43): 5585-5596, 2016 10 27.
Article in English | MEDLINE | ID: mdl-27065333

ABSTRACT

Cartilage oligomeric matrix protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Tissue microarrays derived from two cohorts of patients with breast cancer (n=122 and n=498) were immunostained, revealing varying expression of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and decreased recurrence-free survival. Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdcscid/Rj) mice. Tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control, mock-transfected, tumors. In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of matrix metalloprotease-9. Furthermore, microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. This observation was confirmed in vitro as COMP-expressing cells showed better survival as well as a higher rate of protein synthesis when treated with brefeldin A, compared with control cells. Further, COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect. Thus, in vitro measurement of cell respiration indicated decreased mitochondrial metabolism. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by metabolic switching and increasing invasiveness and tumor cell viability, leading to reduced survival in animal models and human patients.


Subject(s)
Breast Neoplasms/etiology , Breast Neoplasms/metabolism , Cartilage Oligomeric Matrix Protein/metabolism , Cell Transformation, Neoplastic/metabolism , Animals , Apoptosis/genetics , Biomarkers, Tumor , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cartilage Oligomeric Matrix Protein/genetics , Cell Adhesion/genetics , Cell Line , Cell Membrane/metabolism , Cell Movement/genetics , Disease Models, Animal , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , Female , Gene Expression , Gene Expression Profiling , Heterografts , Humans , Immunohistochemistry , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice, SCID , Neoplasm Metastasis , Oxidative Phosphorylation , Prognosis , Proportional Hazards Models , Recurrence
9.
Clin Exp Immunol ; 185(2): 252-62, 2016 08.
Article in English | MEDLINE | ID: mdl-27010233

ABSTRACT

The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation. Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21(-/low) ) are increased in conditions with chronic inflammation, e.g. autoimmune diseases. However, little is known about the CD21(-/low) B cell subset in peripheral blood from healthy donors. Here, we show that CD21(-/low) cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21(-/low) subset can be divided into CD38(-) 24(+) and CD38(-) 24(low) cells, where most of the CD38(-) 24(+) are CD27(+) immunoglobulin (Ig)M(+) IgD(+) and the CD38(-) 24(low) are switched CD27(-) . Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. In contrast to naive cells, the majority of CD21(-/low) cells lack expression of the ABCB1 transporter. Stimulation with a combination of BCR, Toll-like receptor (TLR)-7/8 and interleukin (IL)-2 induces proliferation and differentiation of the CD21(-/low) B cells comparable to CD21(+) CD27(+) memory B cells. The response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naive B cells. This is ascribed to a weaker response by the CD38(-) 24(low) subset, implying that some memory B cells require not only TLR but also BCR triggering. We conclude that the CD21(-/low) cells in healthy donors are memory B cells.


Subject(s)
B-Lymphocyte Subsets/immunology , Immunologic Memory , Receptors, Complement 3d/blood , Receptors, Complement 3d/immunology , ADP-ribosyl Cyclase 1/immunology , ATP Binding Cassette Transporter, Subfamily B/metabolism , Adult , CD24 Antigen/immunology , Cell Differentiation , Female , Flow Cytometry , Healthy Volunteers , Humans , Immunoglobulin D/biosynthesis , Immunoglobulin M/biosynthesis , Interleukin-2/immunology , Lymphocyte Activation , Male , Membrane Glycoproteins/immunology , Middle Aged , Receptors, Antigen, B-Cell/immunology , Toll-Like Receptor 7/immunology , Young Adult
10.
Scand J Urol ; 49(6): 486-491, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26389795

ABSTRACT

OBJECTIVE: The aim of this study was to estimate rates and type of definitive surgical interventions for nephrolithiasis in Swedish patients with ankylosing spondylitis (AS) compared to the general population. MATERIALS AND METHODS: This national prospective cohort study linked data from Swedish population and healthcare registries. Incidence rates and interventions for nephrolithiasis during follow-up in patients with AS were compared to general population comparator (GPC) subjects. RESULTS: In total, 8572 AS patients were followed for 49,959 person-years and 39,639 matched GPCs were followed for 225,221 person-years. Mean age at study entry was 46 years [interquartile range (IQR) 36-56 years] and 65% were male. In AS patients with a diagnosis of nephrolithiasis during the study period, 29% (72/250) underwent similar intervention for nephrolithiasis compared to 24% (114/466) GPCs (p = 0.21). The incidence rate ratio (RR) in overall AS patients was 2.9 [95% confidence interval (CI) 2.1-3.8] during a median follow-up of 6.2 years (IQR 3.2-8.6 years). With prior diagnosis of nephrolithiasis, the RR for AS patients compared to GPCs was 3.7 (95% CI 1.8-7.7); without prior nephrolithiasis the RR was 2.1 (95% CI 1.5-3.0). Increasing age [odds ratio (OR) 1.02, 95% CI 1.01-1.03], prior nephrolithiasis diagnosis (OR 3.3, 95% CI 1.97-5.62) and atherosclerotic cardiac disease (OR 2.0, 95% CI 1.03-3.91) were identified as predictors of intervention for nephrolithiasis. CONCLUSIONS: Patients with AS have an almost three-fold increased risk of surgical intervention for kidney stones, with similar management, compared to the general population.

11.
Scand J Rheumatol ; 44(5): 369-76, 2015.
Article in English | MEDLINE | ID: mdl-25797539

ABSTRACT

OBJECTIVES: Epidemiological studies of spondyloarthritis (SpA), using ICD codes from the Swedish National Patient Register (NPR), offer unique possibilities but hinge upon an understanding of the validity of the codes. The aim of this study was to validate the ICD codes for ankylosing spondylitis (AS) and undifferentiated SpA (uSpA) in the NPR against the established classification criteria [modified New York (mNY), Assessment of SpondyloArthritis international Society (ASAS), Amor, and European Spondyloarthropathy Study Group (ESSG) criteria]. METHOD: All patients with an ICD-8/9/10 code of AS or uSpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine or corresponding hospitalization, alive and living in Sweden 2009, were identified (n=20,089). Following a structured procedure to achieve geographical representativeness, 500 random patients with a diagnosis of AS or uSpA in 2007-2009 were selected. Based on a structured review of clinical records, positive predictive values (PPVs) for fulfilling the criteria sets were calculated. RESULTS: For those having received an ICD code for AS, the PPVs for fulfilling the mNY criteria or any set of SpA criteria were 70% and 89%, respectively. For those with an uSpA diagnosis (and never an AS diagnosis), the corresponding PPVs were 20% and 79%. The subset with both AS and uSpA diagnoses (overlap=12%) were as likely to fulfil the mNY criteria as the group that had been coded as AS only. CONCLUSIONS: The diagnosis codes for AS or uSpA had high PPVs, suggesting that our case identification in the Swedish NPR can be used for nationwide, population-based, epidemiological studies of these diseases.


Subject(s)
Spondylarthritis/diagnosis , Spondylarthritis/epidemiology , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/epidemiology , Adolescent , Adult , Clinical Coding , Cohort Studies , Female , Humans , Incidence , Male , Registries , Retrospective Studies , Spondylarthritis/classification , Spondylitis, Ankylosing/classification , Sweden/epidemiology , Young Adult
12.
Arthritis Care Res (Hoboken) ; 67(8): 1137-49, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25623277

ABSTRACT

OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs. METHODS: We performed a national register-based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987-2009. Treatment exposure was assessed time dependently based on the prescription drug register from 2006-2009, adjusting for sociodemographics and comorbidities derived from national population-based registers. RESULTS: Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal, or renal adverse events were seen among the 3 exposure groups. Patients unexposed to NSAIDs had more baseline comorbidities and an increased relative risk for congestive heart failure events during the study period (2.0, 95% confidence interval [95% CI] 1.3-3.2). The relative risk for atherosclerotic events was nonsignificant when compared to the nonselective NSAID group (1.0, 95% CI 0.7-1.5), while the relative risk for gastrointestinal events was lower for unexposed patients (0.5, 95% CI 0.4-0.7). CONCLUSION: Overall, serious adverse events related to nonselective NSAIDs, etoricoxib, and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerably more baseline comorbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAIDs in clinical practice.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase 2 Inhibitors/adverse effects , Pyrazoles/adverse effects , Pyridines/adverse effects , Spondylarthropathies/drug therapy , Sulfonamides/adverse effects , Sulfones/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/adverse effects , Celecoxib , Cohort Studies , Etoricoxib , Female , Humans , Male , Middle Aged , Registries , Spondylitis, Ankylosing/drug therapy , Sweden , Young Adult
13.
Ann Rheum Dis ; 74(6): 1156-63, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25512675

ABSTRACT

OBJECTIVES: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. RESULTS: Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. CONCLUSIONS: CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01235598.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/drug therapy , Hand Joints/pathology , Immunoglobulin Fab Fragments/therapeutic use , Immunosuppressive Agents/therapeutic use , Osteitis/drug therapy , Polyethylene Glycols/therapeutic use , Synovitis/drug therapy , Adult , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/pathology , Certolizumab Pegol , Double-Blind Method , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Osteitis/etiology , Osteitis/pathology , Synovitis/etiology , Synovitis/pathology , Treatment Outcome
14.
J Chromatogr A ; 1337: 128-32, 2014 Apr 11.
Article in English | MEDLINE | ID: mdl-24630054

ABSTRACT

In this study, a method of determining radiochemical yield and radiochemical purity using radio-HPLC detection employing a dual-flow-cell system is evaluated. The dual-flow cell, consisting of a reference cell and an analytical cell, was constructed from two PEEK capillary coils to fit into the well of a NaI(Tl) detector. The radio-HPLC flow was directed from the injector to the reference cell allowing on-line detection of the total injected sample activity prior to entering the HPLC column. The radioactivity eluted from the column was then detected in the analytical cell. In this way, the sample will act as its own standard, a feature enabling on-line quantification of the processed radioactivity passing through the system. All data were acquired on-line via an analog signal from a rate meter using chromatographic software. The radiochemical yield and recovery could be simply and accurately determined by integration of the peak areas in the chromatogram obtained from the reference and analytical cells using an experimentally determined volume factor to correct for the effect of different cell volumes.


Subject(s)
Radiopharmaceuticals/chemistry , Astatine , Benzoates/chemistry , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Iodine Radioisotopes , Isotope Labeling , Limit of Detection , Technetium , Trimethyltin Compounds/chemistry
17.
Scand J Rheumatol ; 42(2): 123-30, 2013.
Article in English | MEDLINE | ID: mdl-23126587

ABSTRACT

OBJECTIVE: Suggested predictors of rheumatoid arthritis (RA) include environmental exposure, such as smoking. Our purpose was to investigate potential predictors of RA in a nested case-control study based on a prospective cohort. METHOD: Between 1991 and 1996, 30,447 persons were included in the Malmö Diet and Cancer Study (MDCS). Individuals who developed RA after inclusion up to 31 December 2004 were identified by linking the database to different registers. Four controls were selected for every case. Data on lifestyle factors were collected in the MDCS. RESULTS: We identified 172 incident cases of RA [36 men/136 women, mean age at diagnosis 63 years, 69% rheumatoid factor (RF) positive, median time from inclusion to diagnosis 5 (range 1-13) years]. In bivariate analyses, baseline smoking [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.31-3.12] and a low level of formal education (i.e. ≤ 8 years; OR 2.42, 95% CI 1.18-4.93 vs. University degree) predicted subsequent development of RA. Infrequent baseline alcohol consumption was a predictor of RA (OR 3.47, 95% CI 1.91-6.30) compared to recent use (within the past month), and individuals with moderate baseline alcohol consumption (3.5-15.2 g/day vs. < 3.5 g/day) tended to have a reduced risk of RA (OR 0.48, 95% CI 0.22-1.05) in multivariate analyses, adjusted for smoking and level of education. CONCLUSIONS: Smoking and a low level of formal education were found to be independent predictors of RA. Moderate alcohol consumption may also be associated with a reduced risk.


Subject(s)
Alcohol Drinking/adverse effects , Arthritis, Rheumatoid/epidemiology , Educational Status , Smoking/adverse effects , Aged , Case-Control Studies , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk Factors
18.
Scand J Rheumatol ; 41(6): 434-7, 2012.
Article in English | MEDLINE | ID: mdl-22813208

ABSTRACT

OBJECTIVES: To determine the incidence of severe extra-articular rheumatoid arthritis (ExRA) in a community-based cohort of RA patients, and to evaluate whether treatment with tumour necrosis factor (TNF) inhibitors has any effect on the risk of ExRA. METHODS: In a review of clinical records from 1 July 1997 to 31 December 2004, severe ExRA manifestations were classified according to predefined criteria. Patients were censored at the development of ExRA, death, emigration, or 31 December 2004. Exposure to anti-TNF treatment has continuously and independently been recorded as part of a regional follow-up system. RESULTS: During treatment with TNF inhibitors, there were two patients with new onset of ExRA in 408 person-years at risk (pyr) [0.49/100 pyr, 95% confidence interval (CI) 0.06-1.77]. Among those without anti-TNF treatment there were 63 patients with ExRA in 5425 pyr (1.16/100 pyr, 95% CI 0.89-1.49). The relative risk comparing those treated to those not treated with TNF inhibitors was 0.42 (95% CI 0.10-1.73). CONCLUSION: Our data show a lower incidence of ExRA in patients treated with TNF inhibitors but further studies with a larger sample size are needed for a more accurate estimate of the size of the effect.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Pericarditis/epidemiology , Pleurisy/epidemiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Vasculitis/epidemiology , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Pericarditis/complications , Pleurisy/complications , Retrospective Studies , Surveys and Questionnaires , Vasculitis/complications
19.
Scand J Immunol ; 75(5): 510-6, 2012 May.
Article in English | MEDLINE | ID: mdl-22229650

ABSTRACT

The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. The study design was prospective and randomised. Fifty patients undergoing open major colorectal surgery due to cancer disease or inflammatory bowel disease were studied. Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil, and 25 patients were given inhalational anaesthesia with sevoflurane and fentanyl. To determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-a (TNF-a)), interleukin-1b (IL-1b), IL-6, IL-8, IL-4 and IL-10), blood samples were drawn preoperatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins.


Subject(s)
Anesthetics/administration & dosage , Colon/surgery , Complement Activation , Interleukins/biosynthesis , Aged , Anesthesia, Inhalation , Anesthesia, Intravenous , Female , Fentanyl/pharmacology , Humans , Interleukin-10/biosynthesis , Interleukin-10/blood , Interleukin-1beta/biosynthesis , Interleukin-1beta/blood , Interleukin-4/biosynthesis , Interleukin-4/blood , Interleukin-6/biosynthesis , Interleukin-6/blood , Interleukin-8/biosynthesis , Interleukin-8/blood , Male , Methyl Ethers/pharmacology , Middle Aged , Piperidines/pharmacology , Propofol/pharmacology , Remifentanil , Sevoflurane , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/blood
20.
Neuropsychol Rehabil ; 21(3): 383-400, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21480050

ABSTRACT

The objective of the study was to assess sense of coherence (SOC) many years after traumatic brain injury (TBI) and explore the relationship between SOC and self-rated life satisfaction (LS) as well as measures of functioning and disability, sex, age at injury, injury severity and time post-injury. Sixty-six individuals (aged 18-65 years) who were 6-15 years post-injury were interviewed. Data on SOC (SOC-13 item scale), measures of functioning and disability (Mayo-Portland Adaptability Inventory, MPAI-4), LS (Satisfaction with Life Scale, SWLS), and sex, age at injury, injury severity and time post-injury were analysed with hierarchical multiple regression analyses. The results showed that SOC in the study group did not differ from the general population and was strongly associated with LS. Regression analyses revealed that emotional factors, social participation, SOC, and time since injury, were more influential than sex, age at injury, and injury severity in explaining LS. It was concluded that SOC in this group of individuals with TBI who were many years post-injury was similar to nondisabled individuals. SOC, together with emotional factors, social participation and injury-related factors, were determinants of LS. These results confirm that LS after TBI is a complex phenomenon dependent on several factors that are important targets for rehabilitation professionals.


Subject(s)
Adaptation, Psychological , Brain Injuries/psychology , Disability Evaluation , Internal-External Control , Personal Satisfaction , Adult , Brain Injuries/diagnosis , Female , Humans , Male , Middle Aged , Psychomotor Performance , Quality of Life , Self Report , Severity of Illness Index , Sweden , Time Factors
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