The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries.

OBJECTIVES: In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). METHODS: Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009-2011, 2012-2013, 2014-2015, 2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. RESULTS: Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009-2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. CONCLUSION: In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.

Glucose management team significantly improves glycaemic care and commitment to in-hospital guidelines within arthroplastic patients.

BACKGROUND: Perioperative dysglycaemias are a risk for harm but guidelines to improve glucose management are poorly adhered to. AIM: To determine whether a specialized team and diabetes education improves the implementation of guidelines and glucose values. METHODS: We conducted a prospective study of 611 nonselected, consecutive patients attending for elective hip or knee arthroplasty. The first 209 patients received conventional care and the following 402 patients received intervention (Acute Glucose Service, AGS) in two chronological groups; either perioperatively (AGS1) or also preoperatively (AGS2). The AGS-team provided diabetes education, identified the patients with diabetes risk and adjusted the medication when needed. Capillary plasma glucose (CPG) was repeatedly measured and glycated haemoglobin (HbA1c) obtained before and after the surgery. The study objectives were to evaluate the staff actions when hyperglycaemia was severe (CPG >10 mmol/L), and to assess improvement of the glycaemic values and the complication rate within 3 months. RESULTS: None of the severely hyperglycaemic events in the reference group were treated according to guidelines. In the AGS 1 group, 50% and in the AGS2 group, 53% were appropriately managed (p < .001). The events of hyperglycaemia (CPG >7.8 mmol/L at least twice) and of severe hyperglycaemia (CPG >10 mmol/L) decreased in all patient groups. The medians of the highest, mean and variability of CPG values improved. The mean HbA1c improved significantly within AGS 2. There was no association between improved glycaemic care and early complications. CONCLUSIONS: AGS intervention significantly improves adherence to guidelines and glucose values.

Analgesic purchases among older adults - a population-based study.

BACKGROUND: Pain is a frequent and inevitable factor affecting the quality of life among older people. Several studies have highlighted the ineffectiveness of treating chronic pain among the aged population, and little is known about the prevalence of analgesics administration among community-dwelling older adults. The objective was to examine older adults' prescription analgesic purchases in relation to SF-36 pain in a population-based setting. METHODS: One thousand four hundred twenty community-dwelling citizens aged 62-86 years self-reported SF-36 bodily pain (pain intensity and pain-related interference) scores for the previous 4 weeks. The Social Insurance Institution of Finland register data on analgesic purchases for 6 months prior to and 6 months after the questionnaire data collection were considered. Special interest was focused on factors related to opioid purchases. RESULTS: Of all participants, 84% had purchased prescription analgesics during 1 year. NSAIDs were most frequently purchased (77%), while 41% had purchased paracetamol, 32% opioids, 17% gabapentinoids, and 7% tricyclic antidepressants. Age made no marked difference in purchasing prevalence. The number of morbidities was independently associated with analgesic purchases in all subjects and metabolic syndrome also with opioid purchases in subjects who had not reported any pain. DISCUSSION: Substantial NSAID and opioid purchases emerged. The importance of proper pain assessment and individual deliberation in terms of analgesic contraindications and pain quality, as well as non-pharmacological pain management, need to be highlighted in order to optimize older adults' pain management.

Perioperative hyperglycaemia in elective arthroplasties. Should we do better?

BACKGROUND: Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty. METHODS: Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery. Actions of the attending teams to CPG values and detection of patients at risk were analysed. RESULTS: A total of 209 patients were enrolled. All diabetic patients on insulin (6/6) had hyperglycaemia (≥7.8 mmol/l) more than twice and severe hyperglycaemia (>10 mmol/l) at least once. Of the 27 diabetic patients not on insulin 26 (96.3%) had CPG ≥ 7.8 mmol/l ≥ 2 times and 17 (63%) >10 mmol/l. The corresponding figures of the 176 non-diabetic patients were 137 (77.8%) and 61 (34.7%). Severe hyperglycaemia occurred in 54/176 (30.1%) of the non-diabetic patients with pre-operative HbA1c < 42 mmol/mol and random plasma glucose < 7.8 mmol/l. Of the 84 hyperglycaemic episodes > 10 mmol/l, none was treated. Patients with a FINDRISC score ≥ 12 (corresponding to moderate to high risk of diabetes) and hyperglycaemia went unnoticed. CONCLUSIONS: Hyperglycaemia is common among elective orthopaedic surgery patients with or without diabetes. More than 80% of the 209 patients had hyperglycaemia and 40% had severe hyperglycaemia. None of the patients was treated according to guidelines and none of the patients at risk of hyperglycaemia or diabetes was noticed. There is an obvious need for further education and support by diabetes specialists. CLINICAL TRIAL REGISTRATION: Clinical trials, gov. NCT03306810.

Long-term prognostic impact of hyperuricemia in community.

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.

Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two syndromes is warranted.

Pneumonia in children with juvenile idiopathic arthritis in Finland 1999-2014: a nationwide retrospective register linkage study.

OBJECTIVES: To compare the incidence of pneumonia in children with juvenile idiopathic arthritis (JIA) to the aged-matched general population and to evaluate the use of anti-rheumatic medication among children with JIA and pneumonia. METHODS: The National Hospital Discharge Register collects data on ICD-diagnoses of hospital patients in Finland. From this register, patients with JIA under 18 years of age with pneumonia from 1999 through 2014 were identified. The control group consisted of age-matched patients derived from the general population with a diagnosis of pneumonia made in the same calendar year as the pneumonia of the JIA patients. The patient records of the children with JIA were scrutinised for the use of anti-rheumatic medication. RESULTS: We identified 223 pneumonias among the JIA patients (56,161 patient-years) and 53,058 pneumonias in the control group (17,546,609 person-years). The incidence of pneumonia in children with JIA was 386 (annual range 131-639) and in the control group 303 (annual range 225-438) per 100,000 person-years. The incidence of pneumonia increased significantly over time among JIA patients (p=0.013) and in the control group (p<0.001). Through 2007-2014 the rate of pneumonia was significantly higher among children with JIA (p<0.001) than control children. We found 150 JIA patients with pneumonia confirmed by positive chest radiograph. Altogether 47% of the JIA patients had combination medication. The use of methotrexate and biologic agents increased significantly over time (p=0.016 and p<0.001, respectively). CONCLUSIONS: The incidence of pneumonia increased in children with JIA and in the general population from 1999 to 2014. During 2007-2014 JIA patients had a significantly higher rate of pneumonia than age-matched controls. The use of active anti-rheumatic medication was common.

Pessimism, diet, and the ability to improve dietary habits: a three-year follow-up study among middle-aged and older Finnish men and women.

BACKGROUND: Dietary habits have a great influence on physiological health. Even though this fact is generally recognized, people do not eat as healthily as they know they should. The factors that support a healthy diet, on the other hand, are not well known. It is supposed that there is a link between personal traits and dietary habits. Personal traits may also partially explain why some people manage to make healthy dietary changes while some fail to do so or are not able to try to make changes even when they desire to do so. There is some information suggesting that dispositional optimism plays a role in succeeding in improving dietary habits. The aim of this study was to determine the role of optimism and pessimism in the process of dietary changes. METHODS: Dispositional optimism and pessimism were determined using the revised Life Orientation Test in 2815 individuals (aged 52-76 years) participating in the GOAL study in the region of Lahti, Finland. The dietary habits of the study subjects were analysed. After 3 years, the subjects' dietary habits and their possible improvements were registered. The associations between dispositional optimism and pessimism, dietary habits at baseline, and possible changes in dietary habits during the follow-up were studied with logistic regression. We also studied if the dietary habits or certain lifestyle factors (e.g. physical exercising and smoking) at baseline predicted success in improving the diet. RESULTS: Pessimism seemed to correlate clearly negatively with the healthiness of the dietary habits at baseline - i.e. the higher the level of pessimism, the unhealthier the diet. Optimism also showed a correlation with dietary habits at baseline, although to a lesser extent. Those who managed to improve their dietary habits during follow-up or regarded their dietary habits as healthy enough even without a change were less pessimistic at baseline than those who failed in their attempts to improve their diet or did not even try, even when they recognized the need for a change. CONCLUSIONS: Pessimistic people are more likely to eat an unhealthy diet than others. Pessimism reduces independently the possibilities to improve dietary patterns.

Efficacy and effectiveness of tumour necrosis factor inhibitors in the treatment of rheumatoid arthritis in randomized controlled trials and routine clinical practice.

Objective: Efficacy of TNF inhibitors in the treatment of RA assessed in randomized controlled trials (RCTs) may not be fully comparable to routine care owing to the stringent inclusion criteria. The objective of this study was to observe the effectiveness of TNF inhibitors in real-world patients and assess the patients' potential eligibility for the RCTs. Methods: RA patients starting a TNF-inhibitor treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland, which is a longitudinal observational cohort study. Effectiveness was measured using the ACR and EULAR response criteria and by studying the proportion of patients reaching DAS28 remission. The patients' baseline characteristics were compared against the inclusion criteria of 27 RCTs. Results: EULAR moderate and good treatment responses at 6 months were achieved by 69 and 40% of the users of the first TNF inhibitor, respectively. ACR20, ACR50 and ACR70 responses were reached by 48, 27 and 13%, respectively. DAS28 remission was reached by 47%. Only 7.6-44% of the patients would have been potentially eligible for the RCTs. The eligible patients had better treatment responses compared with the non-eligible patients. Different TNF inhibitors were mostly equipotent, but the usage of MTX co-therapy had a major influence on treatment response. Conclusion: Only a small proportion of patients would have been eligible for RCTs, and the efficacy of TNF inhibitors assessed in them cannot be generalized directly into Finnish routine health care.

The spectrum of early rheumatoid arthritis practice across the globe: results from a multinational cross sectional survey.

OBJECTIVES: To explore patterns of real-world early RA (ERA) care across countries. METHODS: An online survey was disseminated to practising rheumatologists across Europe and the US, also made accessible on social media between April and May 2015. Survey questions (n=38) assessed the structure and setting of ERA clinics, times to diagnosis and treatment, patient monitoring, guideline use and data recording. RESULTS: A total of 212 rheumatologists from 39 countries (76% European) completed the survey. 62% had an ERA clinic based at a university hospital. Patient referral to rheumatology was mainly (78%) via primary care; 44% had an agreed ERA local referral pathway, 15% a national pathway. Only 16% had dedicated ERA clinics, the majority being practitioners in Northern Europe with access to a local or national referral pathway. Data for research were collected by 42%. Treatment guidelines were followed by the majority, especially rheumatologists practising in Europe. Variations existed in the use of initial DMARDs with treatment decisions reported to be influenced by international/national guidelines in 71%/61%. No significant relationship between country gross national income and the availability of ERA clinics was seen. CONCLUSIONS: This study provides comparative benchmark information regarding the global provision of ERA care. Substantial variations exist in referral and early assessment pathways with guidelines having a most apparent impact in Northern Europe. Provision of an ERA service does not appear to be constrained by cost, with conceptual factors, e.g. clinician engagement, perhaps playing a role. These initial insights could potentially help harmonise ERA management across countries.

Pessimism and risk of death from coronary heart disease among middle-aged and older Finns: an eleven-year follow-up study.

BACKGROUND: Mortality from coronary heart disease (CHD) remains at quite notable levels. Research on the risk factors and the treatment of CHD has focused on physiological factors, but there is an increasing amount of evidence connecting mental health and personality traits to CHD, too. The data concerning the connection of CHD and dispositional optimism and pessimism as personality traits is relatively scarce. The aim of this study was to investigate the connection between optimism, pessimism, and CHD mortality. METHODS: This was an 11-year prospective cohort study on a regional sample of three cohorts, aged 52-56, 62-66, and 72-76 years at baseline (N = 2815). The levels of dispositional optimism and pessimism of the study subjects were determined at baseline using a revised version of the Life Orientation Test (LOT-R). Eleven years later, those results and follow-up data about CHD as a cause of death were used to calculate odds. Adjustments were made for cardiovascular disease risk. RESULTS: Those who died because of CHD were significantly more pessimistic at baseline than the others. This finding applies to both men and women. Among the study subjects in the highest quartile of pessimism, the adjusted risk of death caused by CHD was approximately 2.2-fold (OR 2.17, 95 % CI 1.21-3.89) compared to the subjects in the lowest quartile. Optimism did not seem to have any connection with the risk of CHD-induced mortality. CONCLUSIONS: Pessimism seems to be a substantial risk factor for death from CHD. As an easily measured variable, it might be a very useful tool together with the other known risk factors to determine the risk of CHD-induced mortality.

No increased cardiovascular mortality among early rheumatoid arthritis patients: a nationwide register study in 2000-2008.

OBJECTIVES: To assess cardiovascular (CV) mortality in early rheumatoid arthritis (RA), and the impact of RA medications on CV mortality. METHODS: We identified all incident RA patients over 18 years of age diagnosed between 2000 and 2007 in Finland. Causes of death were analysed until the end of the year 2008. We used competing-risks regression models to assess the impact of different variables such as RA medications on CV mortality. CV mortality was compared with that of the age- and sex-specific general population. RESULTS: We identified 14,878 incident RA patients (68% women, 63% rheumatoid factor (RF) positive, mean age 55.8/57.5 years in men/women), of whom more than 80% received RA medications for longer than 90% of their individual patient-years. By the end of 2008, 1,157 patients died, 501 (43%) of whom of CV causes. The standardised mortality ratio (SMR) for CV deaths in the entire RA cohort was 0.57 (95% CI 0.52 to 0.62). Along with traditional CV risk factors, the presence of RF and the use of glucocorticoids was associated with a higher risk of CV death, whereas the use of methotrexate was associated with a lower risk. CONCLUSIONS: These nationwide results suggest that patients with recent-onset RA who receive consistent RA medication have no increased risk for CV mortality compared to the general population, at least in the early years of the disease. The use of methotrexate is associated with lower CV mortality, whereas the use of glucocorticoids is associated with a higher than average CV mortality.

Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial.

OBJECTIVE: To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed. RESULTS: Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13). CONCLUSIONS: In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes.

The frequency and outcome of uveitis in patients with newly diagnosed juvenile idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.

OBJECTIVES: To retrospectively compare the frequency and outcome of uveitis between two cohorts of patients with newly-onset juvenile idiopathic arthritis (JIA) separated by a 10 year interval. METHODS: The diagnosis of JIA was made in 239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An ophthalmologist examined all the patients regularly and diagnosed uveitis. The demographics of the patients, type of JIA, frequency, medical treatment and outcome of uveitis were documented. RESULTS: The main outcome measures were the frequency and outcome of uveitis, the number of complications and the best corrected visual acuity (BCVA), need of corticosteroids and other immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in the earlier cohort. The visual outcome was ≥0.5 in all JIA-uveitis patients except one in the earlier cohort. Complications were fewer (21% vs. 35%) and uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN) criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis (20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow-up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the use of methotrexate was equal in both cohorts (65% vs. 67%). CONCLUSIONS: In this study with early and aggressive treatment and close monitoring the outcome of JIA-uveitis patients was favourable and visual loss was avoided in most cases.

Bloodstream infections among children with juvenile idiopathic arthritis: a prospective study from the onset of disease.

OBJECTIVES: To describe the incidence and nature of bloodstream infections (BSI) among children with juvenile idiopathic arthritis (JIA) followed-up prospectively from disease onset. METHODS: The Social Insurance Institution's (SII) national register on individuals with reimbursement for medication of chronic diseases was used to identify children with JIA from 2004 through 2011 and their medications. The National Infectious Disease Register (NIDR) collects data of all blood culture positive samples from all microbiology laboratories in Finland. We combined the NIDR and SII registers to identify JIA patients with BSI. Clinical and laboratory data of each JIA-BSI patient were collected from hospital records. RESULTS: There were 1604 JIA patients and 6630 person-years of follow-up. Five patients had BSI. During the first 5 years after diagnosis the cumulative emergence of BSI was 0.38% [95% confidence interval (CI) 0.16% to 0.92%]. The incidence rates were 7.5/10 000 follow-up years for JIA (95% CI 2.4-17.6) and 2.8/10 000 follow-up years for the age-matched general population (95% CI 2.7-2.9). The standardised incidence ratio was 3.0 (95% CI 1.2 to 7.2). The causative bacteria were Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli and Fusobacterium necrophorum. Three patients were on anti-rheumatic drugs, including two on TNF inhibitors. All patients responded rapidly to antimicrobial therapy and recovered uneventfully. CONCLUSIONS: Although BSI is rare among children with JIA, the incidence is 3-fold higher than among the general population.

Increased risk of levothyroxine-treated hypothyroidism preceding the diagnosis of rheumatoid arthritis: a nationwide registry study.

OBJECTIVES: To evaluate the prevalence of levothyroxine-treated hypothyroidism in rheumatoid arthritis (RA) patients at the time of RA diagnosis in comparison to age- and sex-specific general population. Other objectives were to determine whether the risk of hypothyroidism varies by age at the onset of RA, or by sex or rheumatoid factor (RF) status. METHODS: We identified 7,209 incident RA patients diagnosed between January 2004 and December 2007 from a Finnish nationwide register of special reimbursements for medication costs. The presence of hypothyroidism at RA diagnosis was identified from the same register based on special reimbursement decisions for levothyroxine substitution. The prevalence of levothyroxine-treated hypothyroidism was compared to that of an age- and sex-specific Finnish population, and a standardised rate ratio (SRR) for hypothyroidism was calculated. RESULTS: The SRR for levothyroxine-treated hypothyroidism preceding RA was 1.51 (95% CI 1.35 to 1.67). Neither RF status nor sex modified the risk, although the results did not reach statistical significance among men. The SRR was highest, almost 2.5 among younger female RA patients (20-49 years of age), the excess prevalence of hypothyroidism decreasing steadily and wearing off among patients who were older at the time of diagnosis. The absolute prevalence of hypothyroidism, however, increased with age as it does in the general population. CONCLUSIONS: The risk of hypothyroidism is increased among RA patients already at the disease onset, especially among the young women, regardless of RF status. This calls for attention to screening for hypothyroidism in RA patients, preferably when RA has already been diagnosed.

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. CONCLUSIONS: Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.