Cardiovascular disease-related hospital admissions of patients with inflammatory arthritis.

OBJECTIVE: Patients with inflammatory arthritis (IA) have an increased risk of cardiovascular diseases (CVD), suggesting a high rate of CVD-related hospitalizations, but data on this topic are limited. Our study addressed hospital admissions for CVD in a primary care-based population of patients with IA and controls. METHODS: All newly diagnosed patients with IA between 2001 and 2010 were selected from electronic medical records of the Netherlands Institute for Health Services Research Primary Care database, representing a national network of general practices. Two control patients matched for age, sex, and practice were selected for each patient with IA. Hospital admission data for all patients was retrieved from the Dutch Hospital Data. RESULTS: There were 2615 patients with IA and 5555 controls included in our study. CVD-related hospital admissions were observed more frequently among patients with IA as compared with control patients: 48% versus 36% (p < 0.001) in a followup period of 4 years. Patients with IA were more often hospitalized because of ischemic heart disease (OR 1.7, 95% CI 1.2-2.2) and for day-care admission because of cerebrovascular disease (OR 2.2, 95% CI 1.0-4.9). CONCLUSION: Increased hospital admission rates confirm the higher CVD burden among patients with IA compared with controls, and underscore the need for proper CVD risk management in patients with IA.

Increased risk for chronic comorbid disorders in patients with inflammatory arthritis: a population based study.

BACKGROUND: Studies determining the development of a wide variety of different comorbid disorders in inflammatory arthritis (IA) patients are scarce, however, this knowledge could be helpful in optimising preventive care in IA patients. The aim of this study is to establish the risk that new chronic comorbid disorders in newly diagnosed patients with IA in a primary care setting are developed. METHODS: This is a nested-case-control study from 2001-2010 using data from electronic medical patient records in general practice. In total, 3,354 patients with newly diagnosed IA were selected. Each patient was matched with two control patients of the same age and sex in the same general practice. The development of 121 chronic comorbid disorders of index and control patients was compared using Cox regression. RESULTS: After a median follow-up period of 2.8 years, 56% of the IA-patients had developed at least one chronic comorbid disorder after the onset of IA, compared to 46% of the control patients (p < 0.05). The most frequent developed comorbid disorders after the onset of IA were of cardiovascular (23%), and musculoskeletal (17%) origin. The highest hazard ratios (HRs) were found for anaemia (HR 2.0 [95% CI: 1.4-2.7]) osteoporosis (HR 1.9 [1.4-2.4]), and COPD (HR 1.8 [1.4-2.3]). CONCLUSION: Patients with IA developed more chronic comorbid disorders after the onset of IA than one might expect based on age and sex. Since comorbidity has a large impact on the disease course, quality of life, and possibly on treatment itself, prevention of comorbidity should be one of the main targets in the treatment of IA patients.

The validity of the diagnosis of inflammatory arthritis in a large population-based primary care database.

BACKGROUND: Large population-based databases based on electronic medical records (EMRs) of patients in primary care are a useful data source to investigate morbidity and health care utilization. Diagnoses recorded in EMRs are doctor-defined, but their validity can be disputed. In this study we investigated the validity of the diagnosis inflammatory arthritis (IA), a group of chronic rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, in primary care based EMRs. METHODS: In five general practices, participating in the Netherlands Information Network of General Practice (LINH), EMRs of 219 patients with a diagnostic code of IA were systematically reviewed on characteristics which are not routinely extracted for the LINH database. The diagnosis IA was confirmed when we found, based on a correspondence with a medical specialist, the following diagnoses in the free text fields of the EMR: oligoarthritis, polyarthritis, rheumatoid arthritis and/or spondyloarthropathy. These results were used to determine the validity of the diagnosis IA in EMRs and to develop an algorithm to improve diagnostic validity. RESULTS: From the 219 patients diagnosed as IA in the database, the diagnosis IA was confirmed in 155 patients (70.8%). The algorithm, which resulted in a group of patients with as many as possible confirmed IA-diagnosed patients without excluding too many patients from our dataset, was when patients fulfilled at least one of the following three criteria: 1) a repeat prescription for a disease-modifying antirheumatic drug (DMARD) and/or biological agent, 2) ≥ four contacts or one episode with a diagnostic code for IA, combined with at least two IA-related prescriptions (excluding DMARDs/biological agents), and 3) age at diagnosis ≥ 61 years. After applying this algorithm, the percentage of correctly diagnosed IA patients increased from 71% to 78% reducing the size of our study population by 36%. CONCLUSIONS: Based on additional diagnostic information, the diagnosis IA from EMRs of patients in primary care is sufficiently valid when using the proposed algorithm. After applying the algorithm, the percentage of correctly diagnosed IA patients increased from 71% to 78%.

Prevalence of chronic diseases at the onset of inflammatory arthritis: a population-based study.

OBJECTIVE: Little is known about the presence of chronic morbidity in inflammatory arthritis (IA) patients at disease onset. Previous studies have been mainly performed in established IA patients or they focus on isolated co-morbid diseases. Our aim was to determine the prevalence of chronic diseases at the onset of IA and to determine whether this is different from the number that one might expect based on age and sex. Patients and methods. A nested case-control study from 2001 to 2010 using data from patient electronic medical records in general practice. Totally, 3354 patients with newly diagnosed IA were included. Each patient was matched on age, sex and general practice with two control patients. In total, 121 different chronic diseases were studied. RESULTS: In total, 70% of the IA patients had at least one chronic disease at the onset of IA, compared with 59% of the control patients (P < 0.001). The highest prevalence in IA patients was found for cardiovascular diseases (35%), musculoskeletal diseases (27%) and neurological diseases (22%). Compared with the control patients, patients with IA had the highest increased risk for musculoskeletal diseases [odds ratio, OR = 1.7 (95% confidence interval: 1.6-19)] and for neurological diseases [OR = 1.6 (1.4-1.7)] at the onset of IA. CONCLUSION: At the onset of IA, nearly three-quarters of patients with IA had at least one other chronic disease. Since multi-morbidity affects treatment and outcome of the IA patient, these diseases should be taken into account when treating IA patients.

Do pregnant women contact their general practitioner? A register-based comparison of healthcare utilisation of pregnant and non-pregnant women in general practice.

BACKGROUND: Midwives and obstetricians are the key providers of care during pregnancy and postpartum. Information about the consultations with a general practitioner (GP) during this period is generally lacking.The aim of this study is to compare consultation rates, diagnoses and GP management of pregnant women with those of non-pregnant women. METHODS: Data were retrieved from the Netherlands Information Network of General Practice (LINH), a nationally representative register. This register holds longitudinal data on consultations, prescriptions and the referrals of all patients listed at 84 practices in the Netherlands in 2007-2009, including 15,123 pregnant women and 102,564 non-pregnant women in the same age-range (15 to 45 years). We compared consultation rates (including all contacts with the practice), diagnoses (ICPC-1 coded), medication prescriptions (coded according to the Anatomical Therapeutic Chemical classification system), and rate and type of referrals from the start of the pregnancy until six weeks postpartum (336 days). RESULTS: Pregnant women contacted their GP on average 3.6 times, compared to 2.2 times for non-pregnant women. The most frequently recorded diagnoses for pregnant women were 'pregnancy' and 'cystitis/urinary infection', and 'cystitis/urinary infection' and 'general disease not otherwise specified' for non-pregnant women. The mean number of prescribed medications was lower in pregnant women (2.1 against 4.4). For pregnant women, the most frequent referral indication concerned obstetric care, for non-pregnant women this concerned physiotherapy. CONCLUSIONS: GP consultation rates in pregnancy and postpartum shows that GPs are important providers of care for pregnant women. Therefore, the involvement of GPs in collaborative care during pregnancy and postpartum should be reinforced.

Neurodevelopmental outcome of post-hemorrhagic ventricular dilatation at 12 and 24 months corrected age with high-threshold therapy.

BACKGROUND: The management of post-hemorrhagic hydrocephalus remains a discussion. We describe the neurodevelopmental outcome at the corrected age of 12 and 24 months of infants with PHVD treated with high-threshold therapy. OBJECTIVE: To describe, and compare the neurodevelopmental outcome of a cohort of premature infants with grade III or IV intraventricular hemorrhage with or without development of PHVD. METHODS: Retrospective chart and image review of all IVH grade III and IV infants admitted to the department of Neonatology of the Academic Medical Center, Amsterdam, the Netherlands between January 1999 and December 2006. A standardized neurodevelopmental examination was performed at the corrected ages of 12 and 24 months. RESULTS: In total, 118 cases with IVH were identified. IVH grade III: n = 63, mean gestational age (GA): 28 weeks (SD 2.3), median birth weight (BW): 1130 g (range 908-1460 g); IVH IV: n = 31, mean GA: 28 weeks (SD 2.4), median BW: 1105 g (range 925-1230 g). Grade III and IV cases developed PHVD in 75% versus 42% respectively. Abnormal outcome in IVH III patients mainly occurred in cases with PHVD (12 months: 47% abnormal, 24 months: 64% abnormal). In the IVH IV cases, outcome was comparable with or without PHVD. Developmental delay was more pronounced at 24 months. CONCLUSION: Mainly IVH III cases developed PHVD. Comparing our results with the literature neurodevelopmental outcome was poorer with our high-threshold therapy.

Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight improvement over the 1987 ACR criteria.

BACKGROUND: Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). OBJECTIVE: To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the Visser decision rule. METHODS: 455 patients with early arthritis were studied. The diagnostic performance of the criteria was evaluated using methotrexate treatment within 1 year, expert opinion RA and erosive disease as 'gold standards'. Erosive disease was defined as a 0-3 year change in radiographic score of ≥5. RESULTS: The discriminative ability of the three criteria sets (2010 ACR/EULAR, 1987 ACR criteria and Visser algorithm) was similar with areas under the curve of 0.71-0.78 ('gold standard' methotrexate), 0.74-0.80 (gold standard expert opinion RA) and 0.63-0.67 (gold standard erosive disease after 3 years). The sensitivity of the 2010 ACR/EULAR criteria was highest with 0.85 (gold standard methotrexate). 86% of patients with RA and 51% of 'non-RA' patients according to the new criteria used methotrexate. CONCLUSION: The 2010 ACR/EULAR criteria were slightly more sensitive, but otherwise performed similarly to the older criteria. A high percentage of 'non-RA' patients used methotrexate, the gold standard for RA. The ability of the new criteria to identify patients with erosive disease was low, possibly owing to the effect of intensive treatment.

Predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis.

OBJECTIVES: To identify early predictors of stenosing tenosynovitis in the hand and hand-related activity limitations in patients with rheumatoid arthritis (RA). DESIGN: A longitudinal study of an inception cohort. SETTING: A large outpatient clinic. PARTICIPANTS: Consecutive patients who attended the Early Arthritis Clinic for at least 2 years and fulfilled the American College of Rheumatology criteria for RA at baseline and/or at the 1-year follow-up were invited to participate until 200 patients were included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Stenosing tenosynovitis, assessed by means of a standardized physical examination. Hand-related activity limitations, assessed with the Disabilities of Arm, Shoulder and Hand questionnaire (DASH). A DASH score above the upper limit of the 95% range of the normative score was defined as abnormal. Prognostic factors: demographic and disease activity-related variables, radiographic damage, the Health Assessment Questionnaire (HAQ) total score and category scores at the 2-year follow-up. RESULTS: The mean age ± SD of the patients was 59.7±10.7 years (75% female). The mean time ± SD between the 2-year follow-up and the assessment of the dependent variables was 3.9±2.7 years. Stenosing tenosynovitis was present in 33%. The median (interquartile range) DASH score was 26.7 (10.8-42.5); 30% were abnormal. Stenosing tenosynovitis was predicted by the HAQ subscale regarding the use of hands (HAQ-hand) at the 2-year follow-up (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.2). Hand-related activity limitations were predicted by the Disease Activity Score in 28 joints (OR, 1.8; 95% CI, 1.3-2.4) and HAQ-hand (OR, 2.4; 95% CI, 1.3-5.8) at the 2-year follow-up. CONCLUSIONS: Stenosing tenosynovitis in patients with RA was predicted by HAQ-hand at the 2-year follow-up, and hand-related activity limitations were predicted by disease activity and HAQ-hand at the 2-year follow-up.

Prevalence of hand symptoms, impairments and activity limitations in rheumatoid arthritis in relation to disease duration.

OBJECTIVE: To determine the prevalence of hand and wrist symptoms and impairments, and the resulting activity limitations in relation to disease duration in patients with rheumatoid arthritis. DESIGN AND PATIENTS: A cross-sectional study included 200 consecutive patients with rheumatoid arthritis in 4 categories of disease duration: 2-4, 4-6, 6-8 and ≥ 8 years. Patients were asked about the presence of various hand and wrist symptoms, and underwent a standardized physical examination. To evaluate activity limitations, patients completed the Disabilities of the Arm Shoulder and Hand questionnaire and scored their limitations on a Numerical Rating Scale (0 = no to 10 = maximum limitation). RESULTS: Of all patients, 94% suffered from at least one symptom, and 67% had at least one impairment, mostly from the earliest stages onwards. The median standardized Disabilities of the Arm Shoulder and Hand score (interquartile range) was 26.7 (10.8-42.5). The mean Numerical Rating Scale score for activity limitations was 2.99 (standard deviation 2.50) in the dominant hand and 2.59 (standard deviation 2.49) in the non-dominant hand. CONCLUSION: A high prevalence of hand and wrist symptoms and impairments is often already present after 2 years of disease duration. We recommend that physicians specifically screen for these symptoms and impairments, starting 2 years after the diagnosis of rheumatoid arthritis.

Prediction of walking disability by disease-related factors in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between disease-related factors and walking disability in different phases of rheumatoid arthritis; and to predict future walking disability in rheumatoid arthritis, using disease-related factors assessed 2 years after diagnosis. METHODS: A cohort of 848 newly diagnosed patients with rheumatoid arthritis was followed up for a maximum of 8 years. Walking disability and several disease-related and demographic factors were recorded during follow-up. A logistic regression model was used to study associations between walking disability and these factors at different time points. A multilevel logistic regression model for longitudinal data was used to predict walking disability during follow-up from potential predictors at year 2. RESULTS: Global pain and disease activity were consistently related to walking disability at almost every time point. Significant predictors of future walking disability were: walking disability, knee pain, global pain, the passage of time during follow-up, and age. CONCLUSION: Global pain and disease activity are related to walking disability during the first 8 years of RA. Walking disability, knee pain, and global pain at 2 years follow-up predict walking disability later in the disease. In addition, the risk for walking disability increases during the disease process and with higher age at diagnosis.

IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with radiographic progression in undifferentiated arthritis.

OBJECTIVE: In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA. METHODS: Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score > or = 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) -1031, -863, -857, -308, -238; lymphotoxin-alpha (LTA) +368, +252; interleukin 10 (IL10) -2849, -1082, -819; IL1A -889, IL1B -31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression. RESULTS: Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0-13.1, p < 0.001) and IL10 GGC haplotype (OR 2.8, 95% CI 1.4-5.8, p = 0.003). Mild radiographic progression was associated with the HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1-0.8, p = 0.013) and with allele TNF -308A (OR 0.4, 95% CI, 0.2-0.9, p = 0.02). CONCLUSION: The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF -308A allele, which are associated with mild radiographic progression in early UA.

Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study.

INTRODUCTION: To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status. METHODS: In 545 early arthritis patients ACPA and IgM-RF levels, disease activity (DAS28), the Health Assessment Questionnaire (HAQ) and Sharp/Van der Heijde Score (SHS) were assessed annually. Baseline status, levels and first-year changes of the autoantibodies were associated with these measures at the two-year follow-up and sub-analysed according to autoantibody status. RESULTS: The mean age was 52.7 years, 69% was female, at baseline 56% was ACPA positive, 47% IgM-RF positive. At the two-year follow-up the mean DAS28 was 2.88, and the median HAQ and SHS were 0.38 and 1, respectively. At one year, ACPA and IgM-RF levels had decreased by 31% and 56%, respectively. A switch from negative to positive occurred in 2% for ACPA and 3% for IgM-RF. Positive ACPA and RF status were both associated with SHS at two years (P < 0.001), but baseline levels only showed a minor correlation of ACPA with DAS28 and HAQ at two years. Level changes were not associated with the outcome parameters. CONCLUSIONS: Baseline levels and first-year changes of ACPA and IgM-RF are hardly associated with outcome after two years. Seroconversion seldom occurs. Therefore, it does not appear useful to repeat ACPA or IgM-RF measurements.

Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems.

INTRODUCTION: The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic. METHODS: Levels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients. RESULTS: Seventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA. CONCLUSIONS: ACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation.

Prevalence and course of forefoot impairments and walking disability in the first eight years of rheumatoid arthritis.

OBJECTIVE: To evaluate the prevalence and 8-year course of forefoot impairments and walking disability in patients with rheumatoid arthritis (RA). METHODS: A total of 848 patients with recent-onset RA from 1995 through the present were included. The patients were assessed annually. Pain and swelling of the metatarsophalangeal (MTP) joints, erosions and joint space narrowing of the MTP joints and first interphalangeal joints, and the Health Assessment Questionnaire walking subscale were analyzed using descriptive and correlational techniques. RESULTS: Pain and swelling of > or = 1 MTP joint was present in 70% of patients at baseline, decreasing to approximately 40-50% after 2 years. The forefoot erosion score was > or = 1 in 19% of the patients at baseline, and the prevalence of forefoot erosion increased to approximately 60% after 8 years, during which the mean forefoot erosion score increased from 1.3 to 7.9. At least mild walking disability was present in 57% of patients at baseline, stabilizing at approximately 40% after 1 year. CONCLUSION: The prevalence rates for pain and swelling of the MTP joints and walking disability are initially high and then stabilize, but the prevalence and severity of forefoot joint damage increase during an 8-year course of RA. The findings of this study quantitatively emphasize the importance of forefoot involvement in patients with RA.

Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study.

INTRODUCTION: The aim of our study was to investigate the association between arthritic disease activity and antibodies to mutated citrullinated vimentin (anti-MCV), because such a relation has been suggested. METHODS: Anti-MCV levels were measured in 162 patients with early arthritis (123 with rheumatoid arthritis and 39 with undifferentiated arthritis) at baseline and at 1 and 2 years of follow up. Disease activity was measured using the disease activity score (Disease Activity Score based on 28 joints [DAS28]) and serum C-reactive protein. General estimation equation analysis was used to assess the relation between anti-MCV levels and DAS28 over time. RESULTS: Both, anti-MCV levels and DAS28 exhibited a significant decrease during the first and second year. However, the association between anti-MCV levels and DAS28, adjusted for dependency on sequential measurements within one individual, was very low (beta = 0.00075). In a population of patients with rheumatoid arthritis or undifferentiated arthritis, anti-MCV had a specificity of 92.3% and a sensitivity of 59.3% when using the recommended cut-off of 20 U/ml. Specificity and sensitivity of antibodies against second-generation cyclic citrullinated peptide, using the recommended cut-off value of 25 U/ml, were 92.1% and 55.3%, respectively. Anti-MCV-positive early arthritis patients had significantly higher Sharp-van der Heijde score, erythrocyte sedimentation rate and C-reactive protein levels than did anti-MCV-negative patients at all time points (P < 0.005), but DAS28 was higher in anti-MCV-positive patients at 2 years of follow up only (P < 0.05). CONCLUSION: Because the correlation between anti-MCV levels and parameters of disease activity was very low, we conclude that it is not useful to monitor disease activity with anti-MCV levels.

Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development.

Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA-region contributes most to the genetic risk. HLA-DRB1-molecules containing the amino acid sequence DERAA (i.e., HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302, and *1304) are associated with protection from RA. It has been proposed that not only inherited but also noninherited HLA-antigens from the mother (NIMA) can influence RA-susceptibility. Up to now, no protective NIMAs were described. Here, we studied whether DERAA-containing HLA-DRB1-alleles as NIMA are associated with a protective effect. One hundred seventy-nine families were studied, 88 from the Netherlands and 91 from the United Kingdom. The frequency of DERAA-containing HLA-DRB1-alleles of the Dutch mothers (16.1%), but not of the fathers (26.2%), was lower compared with the general Dutch population (29.3%; P = 0.02). This was replicated in the English set of patients and controls (P = 0.01). Further, of all families, 45 contained at least one DERAA-negative child with RA and at least one DERAA-positive parent. The odds for the DERAA-negative RA patients of having a DERAA-positive mother was significantly lower compared with having a DERAA-positive father (OR 0.25; P = 0.003). These data show a protective NIMA-effect in a human autoimmune disease and indicate that a DERAA-positive mother can transfer protection against RA to her DERAA-negative child.