The heterogeneity of patients meeting American College of Rheumatology (ACR) criteria for a diagnosis of fibromyalgia (FM) challenges our ability to understand the underlying pathogenesis and to optimize treatment of this enigmatic disorder. Our goal was to discern clinically relevant subgroups across multiple psychological and biomedical domains to better characterize the phenomenology of FM. Women meeting 1990 ACR criteria for FM (N=107) underwent psychological (childhood trauma, mood, anxiety, and stress) and biomedical (neuroendocrine, immune, metabolic) testing. Cluster analysis identified four distinct subgroups. Subgroups I, II and III exhibited profiles that included high psychological distress. Subgroup I was further distinguished by a history of childhood maltreatment and hypocortisolism, and these women reported the most pain and disability. Subgroup II evinced more physiological dysregulation and also reported high levels of pain, fatigue, and disability. Subgroup III was characterized by normal biomarkers and reported intermediate pain severity with higher global functioning. Subgroup IV was distinguished by their psychological wellbeing, reporting less disability and pain. Our findings underscore the heterogeneity of both psychological and physiological features among FM patients presenting with nearly identical TP counts. This subgroup categorization is compatible with hypothesized pathogenetic mechanisms of early trauma, stress system dysregulation, and pro-inflammatory bias, each prominent in some but not all FM patients. Appreciation of distinct FM subgroup features is invaluable for selecting the most appropriate treatment modalities.
doi:10.1007/s10067-011-1912-1
PMCID: PMC3603565
PMID: 22200814
Fibromyalgia; Pain; Distress; Maltreatment; Immune; Metabolic; neuroendocrine [6 MeSH terms]
To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.
doi:10.1007/s10067-012-2103-4
PMCID: PMC3558670
PMID: 23090655
Boolean; Criteria; DAS28-ESR; Remission; Tocilizumab
Imagawa, Tomoyuki | Takei, Syuji | Umebayashi, Hiroaki | Yamaguchi, Kenichi | Itoh, Yasuhiko | Kawai, Toshinao | Iwata, Naomi | Murata, Takuji | Okafuji, Ikuo | Miyoshi, Mari | Onoe, Yasuhiro | Kawano, Yoshifumi | Kinjo, Noriko | Mori, Masaaki | Mozaffarian, Neelufar | Kupper, Hartmut | Santra, Sourav | Patel, Gina | Kawai, Shinichi | Yokota, Shumpei
The objective of this study was to evaluate the efficacy, pharmacokinetics, and safety of adalimumab in patients with polyarticular juvenile idiopathic arthritis (JIA) in Japan. Patients aged 4 to 17 years were enrolled in a single-arm, open-label, multicentre study of adalimumab. Patients weighing <30 kg received 20 mg every other week (eow), and those ≥30 kg received 40 mg eow. Concomitant methotrexate (MTX) was allowed (≤10 mg/m2 per week). The primary efficacy outcome was the percent of patients with American College of Rheumatology Pediatric 30 response (ACR Pedi 30) at week 16. JIA core variables, serum adalimumab concentrations, and anti-adalimumab antibodies (AAAs) were analysed. Patients were monitored for adverse events (AEs). Twenty-five patients (20 with concomitant MTX at baseline and 5 without) were enrolled: 24 patients completed 16 weeks of therapy and 22 patients completed 60 weeks. At week 16, 90 % of patients with MTX and 100 % without MTX achieved ACR Pedi 30; response rates were maintained through week 60 in 94 and 80 % of patients, respectively. Each JIA core variable improved over time. Six patients became AAA positive (two each at weeks 8, 16, and 60), some of which were transient. All six AAA-positive patients achieved ACR Pedi 30 at week 16, and four maintained that response at week 60. Six patients (all with MTX) experienced nine serious AEs (JIA, pyrexia, arthralgia, pneumonia, hepatitis B infection, pharyngitis, dehydration, pharyngeal pain, and pneumonia). In pediatric patients with polyarticular JIA in Japan, adalimumab was safe and effective for reducing disease activity for up to 60 weeks.
doi:10.1007/s10067-012-2082-5
PMCID: PMC3505492
PMID: 23053683
Adalimumab; Juvenile idiopathic arthritis; Methotrexate; Pharmacokinetics
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Decreased bone mineral density (BMD) is a common complication of AS, with a prevalence range of 19 to 62 %. Many studies have shown decreased BMD in AS with long disease duration, but only a few studies investigated BMD in early AS. The prevalence of decreased BMD in early disease stages of AS has not yet been clearly described, and for that reason, we reviewed the literature which describes the prevalence of decreased BMD in AS patients with a short disease duration (<10 years). In this review, we included articles which used the modified New York criteria for the diagnosis of AS, included patients with a disease duration of less than 10 years, and used the WHO criteria for osteopenia and osteoporosis. Decreased BMD was defined as a T score < −1.0, including both osteopenia and osteoporosis. For this review, only articles that acquired BMD data of lumbar spine and femoral neck by DXA were used. The literature search provided us 35 articles of which 7 matched all our criteria, and they will be further outlined in this review. The overall prevalence of decreased BMD of the articles reviewed is 54 % (n = 229/424) for lumbar spine and 51 % (n = 224/443) for femoral neck. The prevalence of osteopenia vs. osteoporosis for lumbar spine is 39 vs. 16 % and for femoral neck, 38 vs. 13 %. This review showed a high total prevalence of 51–54 % decreased BMD and 13–16 % osteoporosis in AS with a short disease duration. This high prevalence was not to be expected in a relatively young and predominantly male population. Further research is needed to determine the clinical relevance of this low BMD by investigating the relation between low BMD and vertebral and nonvertebral fractures at this early stage in AS.
doi:10.1007/s10067-012-2018-0
PMCID: PMC3483100
PMID: 22706444
Ankylosing spondylitis; Bone mineral density; Osteopenia; Osteoporosis; Vertebral fractures
Lower extremity ulcers are a recognized complication of rheumatoid arthritis (RA). Their prevalence has not been assessed since the advent of more aggressive disease modifying antirheumatic therapies. The purpose of this study was to establish the period prevalence of lower extremity ulcers in a modern-day unselected cohort of patients with RA, and to report the features associated with ulcer development and response to therapy. Between June 2007 and June 2010, 366 RA patients were evaluated at the Georgetown Division of Rheumatology. Data were collected and analyzed retrospectively on demographics, antibody and prothrombotic profile, comorbidities, disease activity, and outcomes. The period prevalence of ulcers in this cohort of 366 patients with RA followed over 3 years was 4.37%. Patients with ulcers were predominantly female (81.25%) and more commonly African American (56.2%). The mean disease duration at ulcer development was 25.9 years. All patients with ulcers had erosive disease and 63% were seropositive. Only five patients (31.25%) healed over a mean follow-up of 22.8 months. However, in this small sample, treatment with anti-tumor necrosis factor-α (anti-TNFα) therapy was associated with significantly higher likelihood of healing (p=0.039). In this modern-day cohort of patients with RA, we found a prevalence of lower extremity ulcers of 4.37% over 3 years. Only 31.25% of patients healed after a mean 22.8 months of follow-up. However, treatment with a biologic agent was associated with a significant increased likelihood of healing (RR 3.27, 95% CI 0.59–18.29, p=0.039).
doi:10.1007/s10067-011-1710-9
PMCID: PMC3128869
PMID: 21340497
Anti-tumor necrosis factor-α; Disease modifying antirheumatic drug (DMARD); Leg ulcer; Rheumatoid arthritis; Vasculitis; Wound healing
Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.
doi:10.1007/s10067-012-1962-z
PMCID: PMC3362697
PMID: 22367096
IL-13; Diffuse; Localized scleroderma; MMP-1; PBMC; PDGF-BB; Scleroderma
Chiu, Yee | Ostor, Andrew J. K. | Hammond, Anthony | Sokoll, Katharina | Anderson, Marina | Buch, Maya | Ehrenstein, Michael R. | Gordon, Patrick | Steer, Sophia | Bruce, Ian N.
Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an ‘individual funding request’, the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA.
Electronic supplementary material
The online version of this article (doi:10.1007/s10067-011-1936-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s10067-011-1936-6
PMCID: PMC3362712
PMID: 22271229
Abatacept; Individual funding request; National Health Service; National Institute for Health and Clinical Excellence; Rheumatoid arthritis; Tocilizumab
The distressed personality type (“type D personality”) has been shown to be associated with low quality of life and higher morbidity and mortality in various patient groups. Because the role of type D personality is unknown in patients with rheumatoid arthritis (RA), the aim of the present study was to investigate the association of type D personality with aspects of quality of life and disease activity in RA patients. In addition, a potential buffering effect by accepting mindfulness was examined. Participants were 147 patients between 22 and 87 years of age. Patients completed relevant questionnaires at home and the disease activity score was determined. After controlling for potentially confounding variables, multivariate analyses of covariance showed an association of type D personality with a lower satisfaction with life (p < 0.001) and a lower psychological well-being (p < 0.001), but not disease activity in RA patients. Although mindfulness was associated with a higher satisfaction with life (p = 0.02) and positive mood (p = 0.01), it did not diminish the unfavourable associations between type D and well-being. In conclusion, although type D personality is related with lower well-being, it does not seem to be associated with disability or disease activity in RA patients.
doi:10.1007/s10067-011-1905-0
PMCID: PMC3314814
PMID: 22190069
Disease activity; Distressed (type D) personality; Mindfulness; Quality of life; Rheumatoid arthritis; Well-being
Studies on the effectiveness of information provision for patients with arthritis through the Internet are scarce. This study aimed to describe rheumatoid arthritis (RA) patients’ knowledge and information needs before and after launching a website providing information on regional health care services for patients with rheumatic conditions. The intervention consisted of a weekly updated website comprising practical information on regional health care services for patients with arthritis. In addition, patients were offered information leaflets and an information meeting. Before (T1) and 24 months after (T2) the website was launched, a random sample of 400 RA patients filled in a questionnaire regarding knowledge and information need (scores 0–18) about accessibility and contents of 18 regional health care services. Two hundred and fifty-one patients returned the questionnaire (response rate 63%) at T1 and 200 patients (50%) at T2, respectively, with 160 paired observations (112 females (70%), mean age 60.4 years (SD 9.9)). The total score for insufficient knowledge about contents decreased from 9.3 (SD 4.9) to 8.5 (SD 4.8; p = 0.03) and for accessibility from 8.6 (SD 4.7) to 8.4 (SD 4.9; p = 0.59). Total score for information need about contents decreased from 4.2 (SD 4.5) to 1.9 (SD 2.9; p < 0.01) and for accessibility from 3.6 (SD 4.5) to 1.4 (SD 2.4; p < 0.01) (paired t-tests).
After the administration of a website comprising practical health care information, RA patients’ information need and to a lesser extent their perception of having insufficient knowledge on relevant regional health care services decreased significantly. The results of this descriptive study suggest that the use of the Internet to inform patients may be effective, although controlled studies are required to evaluate and optimize web-delivered information.
doi:10.1007/s10067-011-1897-9
PMCID: PMC3314822
PMID: 22160606
Consumer health information; Health care services; Health services accessibility; Information need; Internet; Rheumatoid arthritis
Previous cadaveric studies have suggested that forefoot deformities at the metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) might result from the failure of the ligamentous system and displacement of the plantar plates. This study aimed to examine the relationship between plantar plate pathology and the rheumatoid arthritis magnetic resonance imaging score (RAMRIS) of the lesser (second to fifth) MTP joints in patients with RA using high-resolution 3 T magnetic resonance imaging (MRI). In 24 patients with RA, the forefoot was imaged using 3 T MRI. Proton density fat-suppressed, T2-weighted fat-suppressed and T1-weighted post gadolinium sequences were acquired through 96 lesser MTP joints. Images were scored for synovitis, bone marrow oedema and bone erosion using the RAMRIS system and the plantar plates were assessed for pathology. Seventeen females and 7 males with a mean age of 55.5 years (range 37–71) and disease duration of 10.6 years (range 0.6–36) took part in the study. Plantar plate pathology was most frequently demonstrated on MRI at the fifth MTP joint. An association was demonstrated between plantar plate pathology and RAMRIS-reported synovitis, bone marrow oedema and bone erosion at the fourth and fifth MTP joints. In patients with RA, 3 T MRI demonstrates that plantar plate pathology at the lesser MTP joints is associated with features of disease severity. Plantar plate pathology is more common at the fourth and fifth MTP joints in subjects with RA in contrast to the predilection for the second MTP reported previously in subjects without RA.
doi:10.1007/s10067-011-1899-7
PMCID: PMC3314823
PMID: 22143913
Forefoot; Magnetic resonance imaging; Metatarsophalangeal joint; Plantar plate; RAMRIS; Rheumatoid arthritis
Gouty arthritis is an inflammatory condition associated with debilitating clinical symptoms, functional impairments, and a substantial impact on quality of life. This condition is initially triggered by the deposition of monosodium urate crystals into the joint space. This causes an inflammatory cascade resulting in the secretion of several proinflammatory cytokines and neutrophil recruitment into the joint. While generally effective, currently available agents are associated with a number of adverse events and contraindications that complicate their use. Based on our increased understanding of the inflammatory pathogenesis of gouty arthritis, several new agents are under development that may provide increased efficacy and reduced toxicity.
doi:10.1007/s10067-011-1877-0
PMCID: PMC3249158
PMID: 22069122
Chronic diseases; Gouty arthritis; Inflammation; Pathophysiology
Despite the proven health benefits, patients with rheumatoid arthritis (RA) are found to be less physically active than their healthy peers. The aim of this study was to examine to what extent and how physical activity, defined as any bodily movement resulting in energy expenditure, is currently promoted by health care providers in patients with RA and how they perceive their competencies and educational needs. For this cross-sectional study, Dutch rheumatologists, rheumatology clinical nurse specialists, and expert physical therapists were sent a postal survey including four domains: attitudes towards physical activity in RA, advices given to patients with RA, and perceived competencies and educational needs. A total of 126 rheumatologists (50%), 132 clinical nurse specialists (56%), and 112 physical therapists (53%) returned the questionnaire. More than 90% agreed that physical activity is an important health goal for RA patients and regularly advised their patients to engage in physical activity. Public health recommendations for moderate-intensity physical activity were found attainable in RA patients by 66%, 74%, and 65% and were by used by 19%, 41%, and 49% of them, respectively. On average, respondents rated their competency to promote physical activity as low to medium, and 54%, 85%, and 72% of the respondents expressed a need for additional education regarding this topic. Rheumatologists, nurses, and physical therapists considered regular physical activity to be an important health goal for RA patients. The majority of them commonly gave advice on physical activity but felt not sufficiently competent and indicated a need for additional education.
doi:10.1007/s10067-011-1846-7
PMCID: PMC3218269
PMID: 21912880
Health professionals; Health promotion; Physical activity; Rheumatoid arthritis; Rheumatologists
Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24–73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47–62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance.
doi:10.1007/s10067-011-1792-4
PMCID: PMC3249214
PMID: 21670950
Heart failure; Pulmonary circulation; Right ventricle; Systemic sclerosis
We studied rheumatoid arthritis (RA) patients with foot complaints to address the associations between clinical signs and symptoms, radiographic changes, and function in connection with disease duration. Secondly, we describe the contribution of several foot segments to the clinical presentation and function. In 30 RA patients with complaints of their feet, attributed to either signs of arthritis and/or radiographic damage, we compared radiographic, ultrasound, clinical, and functional parameters of the feet and ankle. Pain and swelling of the ankle were correlated weakly but statistically significantly with limitation and disability (0.273 to 0.293) as measured on the 5-Foot Function Index (FFI). The clinical signs of the forefoot joints did not influence any of the functional outcome measures. Radiographic scores for both forefeet (SvdH) and hindfeet (Larsen) were correlated with the total Health Assessment Questionnaire Disability Index (HAQ DI) and the 5-FFI limitation subscale. Pain and disease duration, more than radiographic damage, influence the total HAQ DI significantly. With the progression of time, structural damage and function of the rheumatic foot worsen in RA patients. Pain and swelling of the ankle contribute more to disability than radiographic damage of the foot and ankle.
doi:10.1007/s10067-011-1780-8
PMCID: PMC3203245
PMID: 21614474
Ankle; 5-FFI; Foot; Function; HAQ; Radiographic damage; Rheumatoid arthritis
Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457–961%) vs 797% (95% CI, 556–1,037%), P = 0.59 and 37% (95% CI, 26–47%) vs 41% (95% CI, 31–50%), P = 0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease.
doi:10.1007/s10067-011-1750-1
PMCID: PMC3145077
PMID: 21484221
Cardiovascular disease; Inflammation; Iontophoresis; Rheumatoid arthritis; Vascular function
The objective of this study is to assess the effectiveness and safety of TNF-α blockers in a group of early psoriatic arthritis (PsA) patients with an unsatisfactory response to previous conventional treatment consecutively enrolled in five Italian centres. A 24-week open-label trial was carried out in consecutive early PsA patients classified according to the CASPAR criteria, with unsatisfactory response to previous treatments and with a DAS28 threshold as ≥3.2, seen at the outpatient clinics of each centre. Exclusion criteria were previous usage of TNF-α blockers and a disease duration >12 months. The choice of any of the three TNF-α blockers was decided by the expert’s opinion, without any restriction. Effectiveness was considered as an improvement of DAS28 at 12 and 24 weeks of treatment. Secondary endpoints were an improvement of TJC, SWJ, HAQ score and PASI score. Changes from baseline to the 12- and 24-week follow-up assessments were analysed using the Wilcoxon paired sign rank test. Twenty-nine patients (14 males, 15 females, median age 37 years, range 20–65 years) were enrolled. A statistical improvement of the DAS28 was observed at 12 and 24 weeks from baseline (p < 0.001). Secondary endpoints also confirmed the effectiveness of the TNF-α blockers in the treatment of early PsA. No severe adverse events were observed during the treatment period, and no patient withdrew from the medications. This study suggests that the TNF-α blockers can be effective in the management of early PsA. Further controlled studies will provide more data on this challenging topic.
doi:10.1007/s10067-011-1680-y
PMCID: PMC3145085
PMID: 21360007
Early disease; EULAR response criteria; DAS28; Psoriatic arthritis; TNF-α blockers
Mindfulness-based interventions are increasingly being used in clinical populations to reduce psychological distress and improve functioning. The Five Facet Mindfulness Questionnaire (FFMQ) is a questionnaire that measures five facets of mindfulness: observe, describe, actaware, nonjudge and nonreact. The goal of this study was to examine the psychometric properties of the FFMQ in a clinical population of fibromyalgia patients. A total of 141 patients completed an online questionnaire on mindfulness (FFMQ) and theoretically related (e.g. acceptance, openness, alexithymia) and unrelated (physical health) constructs. Thirty-eight patients filled in the FFMQ twice. A confirmatory factor analysis (CFA) was conducted to test the five-factor structure of the FFMQ. Internal consistency and test–retest reliability were respectively assessed with Cronbach’s α and intraclass correlation coefficients. Construct validity was examined by correlating FFMQ facets with theoretically related and unrelated constructs. Incremental validity in predicting mental health and psychological symptoms was examined with regression analyses. CFA confirmed the correlated five-factor structure of the FFMQ. Internal consistency of the five facets was satisfactory and test–retest reliability was good to excellent. Construct validity was excellent, as shown by the moderate to large correlations with related constructs (except observe facet) and weak correlation with a theoretically unrelated construct. Two of the five facets (actaware and nonjudge) had incremental validity over the others in predicting mental health and psychological symptoms. After controlling for related constructs, the actaware facet remained a significant predictor. This study showed satisfactory psychometric properties of the Dutch FFMQ in fibromyalgia patients. The observe facet, however, should be used with caution given its deviant relationship with theoretically related constructs.
doi:10.1007/s10067-011-1690-9
PMCID: PMC3145081
PMID: 21347605
Fibromyalgia; Five Facet Mindfulness Questionnaire; Mindfulness; Psychometric characteristics; Self-report assessment
We proposed to assess serum antioxidant vitamins and magnesium (Mg) levels in patients with fibromyalgia (FM) in comparison to healthy controls. Additionally, the association between the serum antioxidant vitamins, magnesium levels, and clinical parameters in FM patients was also investigated. Forty female patients, aged between 30 and 50 years, were diagnosed with FM according to ACR-1990 criteria, and 40 healthy controls were included in the present study. Socio-demographic characteristics of participants, accompanying symptoms, and number of tender points (TP) of the patients were recorded. The intensity of pain was measured using the visual analogue scale (VAS). The functional status and depression levels were evaluated with Fibromyalgia Impact Questionnaire (FIQ) and Beck Depression Inventory (BDI), respectively. Serum vitamins A, C, and E and Mg levels were measured. There were no significant differences in the levels of vitamins A, C, and E and Mg between control subjects and patients with fibromyalgia (p > 0.05). In addition, no statistically significant correlations were found between mean levels of serum vitamins A, C, and E, and Mg and number of TP, scores of VAS, FIQ, and BDI in patients with FM (p > 0.05). According to the results of this study, it was asserted that other complex mechanism may play an important role in the pathophysiology of FM without plasma antioxidant vitamins and Mg levels.
doi:10.1007/s10067-011-1697-2
PMCID: PMC3145090
PMID: 21347604
Antioxidant vitamins; Fibromyalgia; Magnesium; Oxidative stress
Although musculoskeletal disorders are the most common reason for general practitioner visits, training did not keep pace. Implementation of learning from patients with rheumatologic disorders linked together with the teaching of theoretical knowledge in the preclinical medical education might be an important step forward in the improvement of quality of care for these patients. The Leiden Medical School curriculum has implemented two non-obligatory real patient learning (RPL) practicals integrated within the preclinical block musculoskeletal disorders. This study investigates the educational effectiveness of the practicals, the expectations students have of RPL, and students’ satisfaction. Participants’ grades on the end-of-block test served as the test results of the educational effectiveness of the practicals and were compared with those of the non-participants. Qualitative data was collected by means of questionnaires generated by focus groups. The participants in practicals scored significantly higher at the end-of-block test. The expected effects of the contact with real patients concerned positive effects on cognition and skills. ‘Contextualizing of the theory’, ‘better memorizing of clinical pictures’, and ‘understanding of the impact of the disease’ were the most frequently mentioned effects of the practicals. Overall, the participants were (very) enthusiastic about this educational format. The RPL practicals integrated within a preclinical block musculoskeletal disorders are a valuable addition to the Leiden medical curriculum. This relatively limited intervention exhibits a strong effect on students’ performance in tests. Future research should be directed towards the long-term effects of this intervention.
doi:10.1007/s10067-011-1708-3
PMCID: PMC3145092
PMID: 21347603
Focus groups; Medical; Medical education; Musculoskeletal diseases; Patients; Questionnaires; Students; Undergraduate
Early diagnosis of spondyloarthritis (SpA) is essential as anti-tumor necrosis factor therapy can achieve significant symptomatic relief and control of disease activity. This study aims to compare the clinical characteristics, disease activity, and functional status of a Chinese cohort of SpA patients who were re-classified into ankylosing spondylitis (AS) patients fulfilling the modified New York (MNY) criteria, those with undifferentiated SpA (USpA) fulfilling the European Spondyloarthropathy Study Group (ESSG) classification criteria only (USpA/ESSG) and those who fulfill Assessment of SpondyloArthritis International Society (ASAS) only (USpA/ASAS). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), severity of morning stiffness, patient global assessment, and C-reactive protein. Functional status was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI), modified Schober index, and dimension of chest expansion. One hundred and twenty-eight patients with disease duration of 16.3 ± 10.4 years were recruited. Patients in USpA/ESSG and USpA/ASAS were significantly younger (p = 0.01), had shorter disease duration (p < 0.01), and lower BASFI (p = 0.03) than established AS patients. All three groups have active disease with comparable BASDAI >3. BASFI correlated inversely with dimension of chest expansion and negatively modified Schober index in AS patients (p < 0.01) and modestly with BASDAI (r = 0.25, p < 0.01). BASFI correlated moderately with BASDAI in USpA/ESSG (r = 0.61, p < 0.01) but not with chest expansion or modified Schober index. Compared with established AS patients recognized by MNY criteria, patients fulfilling USpA defined by ESSG or ASAS criteria had earlier disease, as active disease and less irreversible functional deficit.
doi:10.1007/s10067-011-1693-6
PMCID: PMC3123457
PMID: 21336823
Classification criteria; Disease activity; Functional status; Spondyloarthropathy
This study aims to examine the needs and preferences regarding the delivery of health care services and information provision and their determinants in patients with systemic sclerosis (SSc). A questionnaire was sent to 77 SSc outpatients, comprising 27 items on health care needs within the domains physical, psychological, social support, employment/daily activities, or other health problems and 13 items on information needs. Moreover, the patients’ preferences regarding the provision of health care services and information were listed. Additional assessments included sociodemographic characteristics, physical functioning (SSc Health Assessment Questionnaire), and quality of life (SF-36). Sixty-four patients (83%) returned the questionnaire. Twenty-six patients (41%) reported one or more unmet health care needs, with the highest proportions of patients with unmet needs seen in the physical (28%) and psychological (20%) domain. The highest percentages of patients with information needs were observed for medical subjects (20–28%). A lower mental component summary scale score and younger age were associated with the presence of at least one health care need in the psychological domain. Worse physical functioning, a diagnosis of diffuse SSc and having a partner were associated with higher information need score. A yearly, standardized multidisciplinary assessment program was most frequently mentioned as a preferred, but not yet existing health care model (59%) and the rheumatologist as a preferred source of information supply (75%). Unmet health care and information needs are common among SSc patients. To improve SSc health care, more attention should be paid to health care services for specific physical and psychological problems and medical information supply by the rheumatologist. In addition, the development of new models of care, such as a yearly, standardized multidisciplinary diagnostic program seems warranted.
doi:10.1007/s10067-010-1645-6
PMCID: PMC3101347
PMID: 21243390
Health care; Systemic sclerosis; Unmet needs
To examine whether patient characteristics predict patient-reported pain and function 2- or 5-years after revision total hip arthroplasty (THA). In a prospective cohort of revision THA patients, we examined whether gender, age, body mass index (BMI), comorbidity (Deyo–Charlson index) and depression predicted moderate–severe hip pain, moderate–severe activity limitation (≥3 activities), dependence on walking aids and use of pain medications, using multivariable regression analysis. Significant predictors of moderate–severe pain at 2- and 5-years were [odds ratio (95% confidence interval)]: female gender, 1.3 (1.0, 1.6) and 1.5 (1.1, 1.9) and age 61–70, 0.7 (0.5, 1.0) and 0.7 (0.5, 1.0; reference (ref),≤60 years). BMI, 30–34.9, 1.4 (1.0, 1.9; ref BMI≤25) and depression, 1.6 (1.0, 2.5) were significantly associated with higher odds of moderate–severe pain at 2 years, but not at 5 years. Significant predictors of nonsteroidal anti-inflammatory drugs (NSAIDs) use 2-years post-revision THA were female gender, 1.4 (1.1, 1.7), BMI, 30–34.9, 1.4 (1.0, 2.0) and age, 71–80, 0.7 (0.5, 0.9). At 5 years, female gender, 1.6 (1.2, 2.2) was significantly associated with NSAID use. Significant predictors of narcotic use 2-years post-revision THA were older age, 61–70, 0.5 (0.3, 0.7) and 71–80, 0.4 (0.3, 0.7) and depression, 2.4 (1.2, 4.6). At 5 years, women, had significantly higher odds 1.8 (1.1, 2.9) of narcotic use and those in age group 61–70 years, significantly lower odds of narcotic use, 0.4 (0.2, 0.7). Similarly, female gender, older age (>70) and BMI of 30 or higher were each significantly associated with higher odds of moderate–severe activity limitation at both, 2- and 5-years. Depression was associated with higher risk at 2 years, 1.7 (1.1, 2.6) and higher Deyo–Charlson score with a higher risk of moderate–severe activity limitation at 5 years, 1.7 (1.1, 2.7). Obesity and depression, considered modifiable clinical factors, were important independent predictors of pain, functional limitation and use of pain medications, following revision THA.
doi:10.1007/s10067-009-1267-z
PMCID: PMC2963019
PMID: 19727914
Body mass index; Comorbidity; Depression; Function; Pain; Pain medications; Predictors; Total hip arthroplasty
Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy.
doi:10.1007/s10067-010-1596-y
PMCID: PMC3052444
PMID: 21046421
Hong Kong; Management; Recommendations; Rheumatoid arthritis
This is a study of the impact of specific and overall comorbidity on health-related quality of life (HRQoL) in men with primary total knee arthroplasty (TKA). In a population-based sample of male veterans who responded to a cross-sectional survey using the validated short-form 36 for veterans (SF-36 V) and had undergone primary TKA prior to survey, eight SF-36 V domain and two summary scores (physical and mental component (PCS and MCS) summary) were compared using multivariable-adjusted multiple linear regressions between patients with and without five comorbidities—chronic obstructive pulmonary disease (COPD)/asthma, diabetes, depression, hypertension, and heart disease. Analyses were adjusted for age, five comorbidities, and time since TKA. Two hundred ninety-three male patients constituted the analytic set with mean (SD) age of 70.3 (8.8) years; 97% were Caucasian and mean (SD) duration since TKA was 2.1 (0.7) years. COPD/asthma was associated with significantly lower adjusted MCS (mean±standard error of mean, 47.1±0.7 vs. 43.1±1.2; p≤0.001) and PCS (30.1±0.6 vs. 27.7±1.0; p<0.05), depression with significantly lower MCS (48.9±0.7 vs. 37.6±1.2; p≤0.001) but not PCS, hypertension with significantly lower MCS (47.0±0.7 vs. 44.3±1.0; p<0.05) but not PCS, and heart disease with significantly lower MCS (47.4±0.8 vs. 44.2±0.9; p≤0.001) and PCS (30.5±0.7 vs. 28.1±0.8; p<0.05). Diabetes was not associated with lower MCS or PCS. The overall number of comorbidities was associated with lower MCS and PCS (p≤0.001 for both). Medical and psychiatric comorbidity impacts physical and mental/emotional HRQoL in patients with primary TKA. The impact differs by comorbidity. Higher comorbidity load negatively impacts both physical and mental/emotional HRQoL.
doi:10.1007/s10067-009-1195-y
PMCID: PMC2950804
PMID: 19449146
Comorbidity; Health-related quality of life; HRQoL; Knee arthroplasty; Quality of life; Total knee arthroplasty
The objective of this study was to compare comorbidity, functional ability, and health care utilization in veterans with total knee arthroplasty (TKA) or total hip arthroplasty (THA) versus matched control populations. A cohort of veterans using Veterans Affairs (VA) healthcare system reported limitations in six activities of daily living (ADLs; bathing, dressing, eating, walking, transferring, and using the toilet), demographics, and physician-diagnosed comorbidity. VA databases provided healthcare utilization and International Classification of Diseases-9/Common procedure terminology codes for TKA/THA. Patients were classified as: (1) primary TKA; (2) primary THA; (3) combination group (≤1 procedure); and (4) control veteran population (no THA/TKA). Multivariable regression analyses compared the risk or counts of ADL limitation and in-/out-patient visits. After multivariable adjustment, TKA, THA or combination groups had significantly higher prevalence of the following compared to veteran controls: arthritis, diabetes, or heart disease (p<0.0001 each), severe (≥3) ADL limitation (33%, 42%, 42% vs. 24%; p<0.0001), and annual hospitalization rate (24%, 19%, 26% vs. 16%, p<0.0001). Annual outpatient surgery visits were more (2.5, 2.3, 2.3 vs. 2, p=0.01) and risk of any mental health outpatient visit was lower (12%, 11%, 12% vs. 18%, p=0.0039). All ADLs, except eating, were significantly more limited in arthroplasty groups (p= 0.0009). Severe ADL limitation was more prevalent in veterans with arthroplasty than in two age-matched US cohorts: 13.4 times in ≥65 years; and 1.2-, 1.6-, and 4-fold in ≥85, 75–84, and 65–74 years. Poorer function and higher comorbidity and utilization in veterans with TKA/THA suggest that this group is appropriate for interventions targeted at improving function and decreasing utilization.
doi:10.1007/s10067-009-1201-4
PMCID: PMC2950866
PMID: 19517157
Arthroplasty; Functional status; Healthcare utilization; Total hip arthroplasty; Total joint arthroplasty; Total knee arthroplasty; Veterans