Factors associated with changes in volumetric bone mineral density and cortical area in men with ankylosing spondylitis: a 5-year prospective study using HRpQCT.

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.

Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

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.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

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.

CD21(-/low) B cells in human blood are memory cells.

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.

Vocational outcome 6-15 years after a traumatic brain injury.

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.

MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16.

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.

Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register.

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.

Smoking, low formal level of education, alcohol consumption, and the risk of rheumatoid arthritis.

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.

Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention.

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.

Complement activation and interleukin response in major abdominal surgery.

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.

Extra-articular manifestations in a community-based sample of patients with rheumatoid arthritis: incidence and relationship to treatment with TNF inhibitors.

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.

Prevalence of spondyloarthritis and its subtypes in southern Sweden.

OBJECTIVE: To estimate the prevalence of spondyloarthritis and its subtypes. METHODS: The Swedish healthcare organisation comprises a system where all inpatient and outpatient care is registered by a personal identifier. For the calendar years 2003-7, all residents aged ≥ 15 years in the southernmost county of Sweden (1.2 million inhabitants) diagnosed by a physician with spondyloarthritis (ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory arthritis associated with inflammatory bowel disease (Aa-IBD) or undifferentiated spondylarthritis (USpA)) were identified. To obtain valid point estimates of prevalence by the end of 2007, identification numbers were cross-referenced with the population register to exclude patients who had died or relocated. RESULTS: The authors estimated the prevalence of spondyloarthritis (not including chronic reactive arthritis) as 0.45% (95% CI 0.44% to 0.47%). The mean (SD) age of patients with prevalent spondyloarthritis by the end of 2007 was 53 (15) years. Among the component subtypes, PsA accounted for 54% of cases, AS 21.4%, USpA 17.8% and Aa-IBD 2.3% with a prevalence of 0.25%, 0.12%, 0.10% and 0.015%, respectively. The remaining 6.4% had some form of combination of spondyloarthritis diagnoses. The prevalence of spondyloarthritis at large was about the same in men and women. However, the subtype PsA was more prevalent in women and AS was more prevalent in men. CONCLUSION: In Sweden the prevalence of spondyloarthritis leading to a doctor consultation is not much lower than rheumatoid arthritis. PsA was the most frequent subtype followed by AS and USpA, and the two most frequent subtypes PsA and AS also display some distinct sex patterns.

Generalisability of clinical registers used for drug safety and comparative effectiveness research: coverage of the Swedish Biologics Register.

OBJECTIVE: To determine coverage and generalisability of data in the Swedish Biologics Register ARTIS. METHODS: Patients with adult onset rheumatoid arthritis (RA) were identified in the National Patient Register and the Swedish Rheumatology Quality Register, including the ARTIS cohort of patients exposed to biological agents. Exposure to etanercept and adalimumab between 2006 and 2008 was determined by register linkage to the Prescribed Drug Register which contains patient-level data on >99% of all etanercept and adalimumab use in Sweden. RESULTS: Of 62 897 patients with RA, 6510 had received treatment with etanercept or adalimumab according to the Prescribed Drug Register. Of these, 5673 were also registered in ARTIS, resulting in a national coverage of 87%. The regional variation was small with >85% coverage in 18 of 21 counties. In multivariable analysis, ARTIS-registered and non-registered patients did not differ by age (p=0.62), sex (p=0.84) or education level (p=0.24). CONCLUSION: Nationwide drug dispensing and demographic data may function as quality metrics for coverage and generalisability assessments. Using such data, the coverage of ARTIS was estimated at 87% with no indications of compromised external generalisability regarding demography.

Changes in body composition after 2 years with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD). Possible predictors for CVD are early changes in body composition. We therefore evaluated changes in lean body mass (LBM), lean mass of arms and legs (LMAL), total body fat mass (BFM), and truncal fat distribution (FD) after 2 years with RA and possible predictors. METHODS: We registered 63 (45 women) RA patients with disease duration of ≤ 12 months at baseline and after 2 years. Disease Activity Score using 28 joint counts (DAS28), Health Assessment Questionnaire (HAQ) score, body mass index (BMI), comorbidities, smoking, and medications were recorded. Total and regional lean mass and fat mass were measured with dual energy X-ray absorptiometry (DXA). The data were compared with 63 age- and gender-matched controls. RESULTS: LBM and LMAL at baseline in RA patients were significantly lower in men (p = 0.020 and 0.002, respectively) compared to matched controls. Truncal FD was non-significantly increased in RA patients (women p = 0.133, men p = 0.119). The age-related deterioration with decreased LBM after 2 years (p = 0.002 in women and men) and increased BFM (p < 0.001) and truncal FD (p = 0.020) in women were all significantly less pronounced in RA patients than in matched controls. CONCLUSIONS: In patients with early RA and after initiation of therapy, the age-related deterioration with decreasing LBM and increasing truncal FD was lower than in control subjects in this observational study. These potentially harmful alterations seem to be modifiable factors in patients with early RA.

The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years.

OBJECTIVE: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome. METHODS: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0-448). RESULTS: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression. CONCLUSION: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.

Sense of coherence and disability and the relationship with life satisfaction 6-15 years after traumatic brain injury in northern Sweden.

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.

Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006.

UNLABELLED: The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. OBJECTIVE: To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. METHODS AND PATIENTS: A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37,024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. RESULTS: During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. CONCLUSIONS: MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.

Rapid and sustained health utility gain in anti-tumour necrosis factor-treated inflammatory arthritis: observational data during 7 years in southern Sweden.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondylarthritides impose a great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry-independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing tumour necrosis factor (TNF) blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures and to compare them across diagnostic entities. METHODS: EuroQoL 5 dimensions (EQ-5D) utility data were collected from a structured clinical follow-up programme of anti-TNF-treated patients with RA (N = 2554), PsA (N = 574) or spondylarthritides (N = 586). Time trends were calculated. Completer analysis was used. RESULTS: There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and spondylarthritides. The maximum gain in utilities had already occurred after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. The first and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and spondylarthritides over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and spondylarthritides. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.

A more active treatment has profound effects on the health status of rheumatoid arthritis (RA) patients: results from a population-based RA register in Malmö, Sweden, 1997-2005.

OBJECTIVE: Population-based studies on the trends and effects of modern antirheumatic treatment are scarce. The aim of this study was to examine trends in treatment, health-related quality of life (HRQL), and disease outcome in a population-based register of patients with rheumatoid arthritis (RA) in Malmö, Sweden. METHODS: A continuously updated population-based RA register was established in the city of Malmö, southern Sweden, in 1997. Self-completed postal questionnaires issued in 1997, 2002, and 2005 were used to collect information on demographics, medication, and health status. Cross-sectional comparisons were made between data from 1997, 2002, and 2005. RESULTS: Between 1997 and 2005, the proportion of patients treated with any disease-modifying anti-rheumatic drug (DMARD) including biologics increased substantially (from 52% to 87%), as well as the proportion treated with methotrexate (from 23% to 52%) and biologics (almost exclusively tumour necrosis factor inhibitors) (from 0% to 20%). Twelve per cent of RA patients received biologics 5 years from disease onset in 2005. In parallel with changes in treatment, mean Health Assessment Questionnaire (HAQ) scores (1.19 vs. 0.89) and all Short Form 36 (SF-36) subscales improved from 1997 to 2005 (non-overlapping confidence intervals). CONCLUSION: Between 1997 and 2005, there was a substantial increase in the use of DMARDs, which was accompanied by improved mean HAQ and SF-36 scores in cross-sectional comparisons. These results support the concept that more intensive treatment with DMARDs and biologics can have profound effects on the overall health status in RA patients at the population level.