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1.  Patient perceptions about illness self-management in ANCA-associated small vessel vasculitis 
Rheumatology (Oxford, England)  2008;47(6):881-886.
Objectives
To characterize patient perceptions, related to eight self-management behaviours relevant for adults with ANCA-associated small vessel vasculitis (ANCA-SVV), and to determine if these perceptions were associated with performance of each behaviour.
Methods
Adults with ANCA-SVV (n=202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients’ perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders.
Results
With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management.
Conclusion
This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.
doi:10.1093/rheumatology/ken126
PMCID: PMC4084613  PMID: 18403403
Antineutrophil cytoplasmic antibodies-associated vasculitis; Self-management; Adherence; Health behaviour; Barriers
2.  Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management 
Rheumatology (Oxford, England)  2013;52(6):968-985.
A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.
doi:10.1093/rheumatology/ket007
PMCID: PMC3651616  PMID: 23445662
DXA; BMD; high bone mass; osteopetrosis; osteoarthritis
3.  FCGR3B copy number variation is associated with systemic lupus erythematosus risk in Afro-Caribbeans 
Rheumatology (Oxford, England)  2011;50(7):1206-1210.
Objectives
To evaluate FCGR3B copy number variation (CNV) in African and European populations and to determine if FCGR3B copy number is associated with SLE and SLE nephritis risk in Afro-Caribbeans, adjusting for African genetic ancestry.
Methods
We estimated FCGR3B to determine if there were ethnic variations in CNV (unrelated unadmixed Europeans and Africans). We then examined CNV at FCGR3B in relation to SLE and SLE nephritis within a case–control collection of 134 cases of SLE (37 with SLE nephritis) and 589 population controls of mainly Afro-Caribbean descent resident in Trinidad.
Results
We found a significant difference in copy number FCGR3B distribution between unadmixed African and European UK cohorts, with 27 (29%) vs 3 (5%) for those with low (0 or 1) copy FCGR3B, respectively, P = 0.002. In a Trinidadian SLE case–control study, low FCGR3B CNV was associated with SLE risk 1.7 (95% CI 1.1, 2.8), P = 0.02, which remained after adjustment for African genetic ancestry; odds ratios (ORs) 1.7 (95% CI 1.0, 2.8), P = 0.04.
Conclusion
Our studies suggest that FCGR3B low copy number is associated with SLE risk in Afro-Caribbean populations independently of CNV due to African ancestry.
doi:10.1093/rheumatology/keq456
PMCID: PMC3670581  PMID: 21296850
SLE; Admixture; FCGR3B; Copy number variation; African
4.  ‘Friend or Foe’: high bone mineral density on routine bone density scanning (DXA), a review of causes and management 
Rheumatology (Oxford, England)  2013;52(6):968-985.
A finding of high bone mineral density (BMD) on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced.
Here we outline a classification for the causes of raised BMD, based upon identification of focal or generalised BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained High Bone Mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.
doi:10.1093/rheumatology/ket007
PMCID: PMC3651616  PMID: 23445662
DXA; BMD; high bone mass; osteopetrosis; osteoarthritis
5.  Antiphospholipid antibodies are associated with enhanced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model 
Rheumatology (Oxford, England)  2005;44(10):1238-1244.
Objective
Oxidative stress contributes to atherosclerosis, and evidence of enhanced oxidative stress exists in antiphospholipid syndrome (APS). In a non-lupus murine model, we evaluated whether anticardiolipin (aCL) antibodies could affect the oxidant/antioxidant balance as an early biochemical step of APS.
Methods
Hybridomas producing human and murine aCL and anti-β2-glycoprotein I (aβ2-GPI) monoclonal antibodies were injected into three groups of five female BALB/c severe combined immunodeficiency (SCID) mice. Corresponding hybridomas secreting non-antiphospholipid antibodies of the same isotype were employed as controls. Sera and organs were collected after 30 days. Paraoxonase (PON) activity, peroxynitrite, superoxide, nitric oxide (NO) and nitrotyrosine were measured in plasma. Expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) was assessed by western blot and immunohistochemistry.
Results
PON activity and NO (sum of nitrate and nitrite) levels were reduced in the human aCL IgG group (P<0.002 and P<0.04, respectively), whilst peroxynitrite and superoxide and expression of total antioxidant capacity of plasma were increased (P<0.01). PON and NO were decreased in the murine aβ2-GPI IgG and IgM aCL groups (P<0.03 and P<0.05, respectively). Nitrotyrosine was elevated in the human aCL IgG group (P<0.03). Western blotting showed reduced iNOS expression in the hearts of the IgG aCL group, confirmed by immunostaining. PON inversely correlated with IgG aCL titres (P<0.001), superoxide (P<0.008) and peroxynitrite levels (P<0.0009). Peroxynitrite and total IgG aCL were independent predictors of PON (P<0.0009 and P<0.02, respectively). Superoxide was the only independent predictor of NO (P<0.008) and of nitrotyrosine (P<0.002).
Conclusion
aCL antibodies are associated with the decreased PON activity and reduced NO that may occur in the preclinical phase of APS.
doi:10.1093/rheumatology/keh722
PMCID: PMC3465365  PMID: 15987712 CAMSID: cams2349
Antiphospholipid antibodies; Oxidative stress; Nitric oxide; Total antioxidant capacity; Paraoxonase
6.  The persistence of anticardiolipin antibodies is associated with an increased risk of the presence of lupus anticoagulant and anti-β2-glycoprotein I antibodies 
Rheumatology (Oxford, England)  2006;45(9):1116-1120.
Objective
We studied antiphospholipid antibodies (aPL) in blood samples from a cohort of individuals followed for thrombosis to determine whether the persistent presence of anticardiolipin antibodies (aCL) is associated with a greater likelihood of having lupus anticoagulant and/or anti-β2-glycoprotein I antibodies (LA/aβ2GPI).
Methods
Blood samples from 353 individuals who had been tested for aCL on at least two occasions were tested for aβ2GPI and LA. Two groups were defined: aCL-persistent, who tested aCL-positive on at least two occasions, and aCL non-persistent, who tested aCL-positive on fewer than two occasions. Multivariate logistic regressions were performed using LA/aβ2GPI, LA and aβ2GPI as outcome variables and the percentage of aCL-positive tests as the predictor variable, adjusted for age, gender, family history of cardiovascular disease (CVD), systemic lupus erythematosus (SLE), smoking and number of venous (VT) and arterial thromboses (AT).
Results
Sixty-eight (19%) individuals were aCL persistent and 285 (81%) were aCL non-persistent. LA/aβ2GPI was found in 36 (53%) of the aCL persistent group and 38 (13%) of the aCL non-persistent group. The two groups were similar for age, gender and smoking. Family history of CVD, SLE, VT and AT were more frequent in the aCL persistent group. Multivariate analyses revealed that odds ratios for LA/aβ2GPI, LA and aβ2GPI were 1.34 [95% confidence interval (CI)=1.22–1.47], 1.36 (95% CI=1.24–1.50) and 1.47 (95% CI=1.31–1.65) respectively for each 10% increase in aCL-positive tests vs 0% positive tests.
Conclusion
Persistence of aCL positivity is associated with an increased risk of LA/aβ2GPI.
doi:10.1093/rheumatology/kel050
PMCID: PMC3435425  PMID: 16510527 CAMSID: cams2311
Antiphospholipid antibodies; Anticardiolipin antibodies; Lupus anticoagulant; Anti-β2-glycoprotein I antibodies
7.  OCCUPATION AND EPICONDYLITIS: A POPULATION-BASED STUDY 
Rheumatology (Oxford, England)  2011;51(2):305-310.
Objectives
To explore the relationship between occupational exposures and lateral and medial epicondylitis and the effect of epicondylitis on sickness absence in a population sample of working aged adults.
Methods
This was a cross-sectional study of 9696 randomly selected adults aged 25-64 years involving a screening questionnaire and standardised physical examination. Age- and sex-specific prevalence rates of epicondylitis were estimated and associations with occupational risk factors explored.
Results
Among 6038 respondents, 636 (11%) reported elbow pain in the last week. 0.7% of those surveyed were diagnosed with lateral epicondylitis and 0.6% with medial epicondylitis. Lateral epicondylitis was associated with manual work (OR 4.0, 95% CI 1.9-8.4). In multivariate analyses, repetitive bending/straightening elbow > 1 hour day was independently associated with lateral (OR 2.5, 95% CI 1.2-5.5) and medial epicondylitis (OR 5.1, 95% CI 1.8-14.3). 5% of adults with epicondylitis took sickness absence because of their elbow symptoms in the past 12 months (median 29 days).
Conclusions
Repetitive exposure to bending/straightening the elbow was a significant risk factor for medial and lateral epicondylitis. Epicondylitis is associated with prolonged sickness absence in 5% of affected working-aged adults.
doi:10.1093/rheumatology/ker228
PMCID: PMC3427015  PMID: 22019808
lateral epicondylitis; medial epicondylitis; epidemiology; occupation; sickness absence
8.  Effectiveness of community- and workplace-based interventions to manage musculoskeletal-related sickness absence and job loss – a systematic review 
Rheumatology (Oxford, England)  2011;51(2):230-242.
This systematic review assesses the effectiveness of interventions in community and workplace settings to reduce sickness absence and job loss in workers with musculoskeletal disorders (MSDs). Relevant studies (randomised controlled trials (RCTs) and cohort studies published since 1990) were identified by screening citations in 35 earlier systematic reviews and from searches of Medline and Embase to April 2010. Among 42 studies (54 reports) including 34 RCTs, 27 assessed return to work, 21 duration of sickness absence, and five job loss. Interventions included exercise therapy, behavioural change techniques, workplace adaptations and provision of additional services. Studies were typically small (median sample size 107 (inter-quartile range (IQR) 77 to 148) and limited in quality. Most interventions were reported as beneficial: the median relative risk (RR) for return to work was 1.21 (IQR 1.00 – 1.60) and that for avoiding MSD-related job loss, 1.25 (IQR 1.06-1.71); the median reduction in sickness absence was 1.11 (IQR 0.32 to 3.20) days/month. However, effects were smaller in the larger and better quality studies, suggesting publication bias. No intervention was clearly superior to others, although effort-intensive interventions were less effective than simple ones. No cost-benefit analyses established statistically significant net economic benefits. Given that benefits are small and of doubtful cost-effectiveness, employers’ practice should be guided by their value judgements about the uncertainties. Expensive interventions should be implemented only with rigorous cost-benefit evaluation planned from the outset. Future research should focus on the cost-effectiveness of simple low cost interventions, and further explore impacts on job retention.
doi:10.1093/rheumatology/ker086
PMCID: PMC3276837  PMID: 21415023
Occupational Disease; Epidemiology; Rehabilitation; Systematic review; Psychological techniques; Physiotherapy
9.  Pro- and anti-fibrotic effects of TGF-β in Scleroderma 
Rheumatology (Oxford, England)  2008;47(Suppl 5):v5-v7.
The University of California at Davis 200 and 206 (UCD-200/206) lines of chickens have proven to be the animal model that best reflects the situation in human systemic sclerosis (SSc). We have demonstrated a disbalance of profibrotic (TGF-β1) and anti-fibrotic (TGF-β2 and 3) TGF-β isoforms as a possible cause for fibrotic alterations in this model. This opens new avenues for diagnosis and therapy for this still intractable condition.
doi:10.1093/rheumatology/ken275
PMCID: PMC3292795  PMID: 18784145
11.  A role for the integrin α6β1 in the differential distribution of CD4 and CD8 T-cell subsets within the rheumatoid synovium 
Rheumatology (Oxford, England)  2008;47(9):1329-1334.
Objective
CD4 and CD8 T-cell subsets accumulate in distinct microdomains within the inflamed rheumatoid synovium. The molecular basis for their differential distribution remains unclear. Since chemokines and adhesion molecules play an important role in the positioning of leucocytes at sites of inflammation, we tested the hypothesis that the differential expression and function of chemokine and/or adhesion molecules explains why CD4+ T cells accumulate within perivascular cuffs, whereas CD8+ T cells distribute diffusely within the tissue.
Methods
Expression of an extensive panel of chemokine receptors and adhesion molecules on matched CD4+ and CD8+ T cells from peripheral blood (PB) and synovial fluid (SF) was analysed by multicolour flow cytometry. Migration assays and flow-based adhesion assays were used to assess the functional consequences of any differences in the expression of chemokine and adhesion receptors.
Results
CD4+ and CD8+ T cells from PB and SF expressed unique yet consistent patterns of chemokine and adhesion receptors. SF CD8+ T cells were much less promiscuous in their expression of chemokine receptors than SF CD4+ T cells. The α6β1 integrin was highly expressed on PB CD4+ T cells, but not on PB CD8+ T cells. Laminin, the ligand for α6β1, retained CD4+ T cells, but less so CD8+ T cells, within inflamed synovial tissue.
Conclusion
Infiltrating PB CD4+ T cells, but not CD8+ T cells, express functional levels of the α6β1 integrin. We propose that this leads to their retention within the rheumatoid synovium in perivascular cuffs, which are defined and delineated by the expression of laminin.
doi:10.1093/rheumatology/ken263
PMCID: PMC3130130  PMID: 18635598
T cells; Alpha 6 integrin; Chemokine receptors; Rheumatoid arthritis
12.  Endothelial cells, fibroblasts and vasculitis 
Rheumatology (Oxford, England)  2005;44(7):860-863.
One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-α and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-α and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.
doi:10.1093/rheumatology/keh542
PMCID: PMC3119433  PMID: 15644388
Vasculitis
13.  Fatigue: a principal contributor to impaired quality of life in ANCA-associated vasculitis 
Rheumatology (Oxford, England)  2010;49(7):1383-1390.
Objectives.
To describe quality of life (QoL) in an ANCA-associated vasculitis (AAV) cohort and make comparisons with a general population sample. In addition, we aimed to take preliminary steps to identify potential disease and psycho-social factors which may determine QoL impairment.
Methods.
A population-based case–control study was designed. All AAV patients resident in Grampian, Scotland, were invited to participate as cases. Controls were identified from a random sample of persons registered with four local general practices. Participants completed a questionnaire comprising validated generic and symptom-specific tools in the assessment of QoL. In addition, all cases were clinically assessed and putative disease factors recorded. Cases and controls were compared and, in addition, disease and psycho-social associations were explored for identified QoL impairments.
Results.
In total, 74/90 (82%) cases and 781/2000 (39%) controls participated. Cases reported a significant impairment in physical health (P < 0.0001), but not mental health (P = 0.85), compared with controls, as measured by Short Form-8 (SF-8). Following adjustment for age and sex, persons with AAV were more than twice as likely to report mild/moderate fatigue [odds ratio (OR) 2.0; 95% CI 1.1, 3.8] or severe fatigue (OR 2.5; 95% CI 1.4, 4.5) compared with controls. Furthermore, among cases, fatigue was found to be strongly associated with impaired physical health (P < 0.0001), while disease factors such as disease activity and damage were not (P = 0.60 and 0.27, respectively).
Conclusions.
Patients with AAV report impaired physical but not mental health. Specifically, fatigue is a principal complaint and appears to be a major determinant of impaired QoL.
doi:10.1093/rheumatology/keq098
PMCID: PMC3091420  PMID: 20400759
ANCA-associated vasculitis; Wegener’s granulomatosis; Microscopic polyangiitis; Churg–Strauss syndrome; Vasculitis; Quality of life; Fatigue
14.  Lateral back pain identifies prevalent vertebral fractures in post-menopausal women: cross-sectional analysis of a primary care-based cohort 
Rheumatology (Oxford, England)  2009;49(3):505-512.
Objective
Vertebral fractures (VFs) are frequently under-recognized, reflecting their lack of diagnostic clinical features. For example, although VFs are associated with back pain, this is also common in the general population. To establish whether back pain can be used to recognize patients with VF, we investigated the site of pain in people with and without VFs using a simple tool.
Methods
A cohort of 504 post-menopausal women was recruited from primary care in South West UK. Back pain was assessed by self-completion of the Margolis pain diagram, and analysis was modified to assess whether pain was mid-line or lateral. VFs were diagnosed by the algorithm-based qualitative method on radiographs. A cross-sectional analysis was carried out to assess the association between back pain and VFs.
Results
Three hundred and twenty-two women (64.1%) reported back pain over the last 12 months. Thirty seven (7.3%) had one or more VFs. In women with back pain, the presence of lateral waist area pain was associated with a 4.5-fold increased risk of VFs [odds ratio (OR) 4.48; 95% CI 2.02, 9.94; P<0.001].
Conclusions
In post-menopausal women with back pain, the presence of lateral waist pain, as shown on the Margolis pain diagram, may identify women at higher risk of prevalent VF.
doi:10.1093/rheumatology/kep414
PMCID: PMC2895162  PMID: 20015975
Back pain; Margolis pain diagram; Vertebral fractures
15.  Arthritis risk after acute bacterial gastroenteritis 
Rheumatology (Oxford, England)  2008;47(2):200-204.
Objectives
Reactive arthritis may occur from bacterial gastroenteritis. We studied the risk of arthritis after an outbreak of Escherichia coli O157:H7 and Campylobacter species within a regional drinking water supply to examine the relationship between the severity of acute diarrhea and subsequent symptoms of arthritis.
Methods
Participants with no known history or arthritis before the outbreak participated in a long-term follow-up study. Of the 2299 participants, 788 were asymptomatic during the outbreak, 1034 had moderate symptoms of acute gastroenteritis, and 477 had severe symptoms, which necessitated medical attention. The outcomes of interest were new arthritis by self-report and a new prescription of medication for arthritis during the follow-up period.
Results
After a mean follow-up of 4.5 years after the outbreak, arthritis was reported in 15.7% of participants who had been asymptomatic during the outbreak, and in 17.6% and 21.6% of those who had moderate and severe symptoms of acute gastroenteritis respectively (p for trend =0.009). Compared with the asymptomatic participants, those with moderate and severe symptoms of gastroenteritis had an adjusted relative risk of arthritis of 1.19 (95% confidence interval [CI] 0.99–1.43) and 1.33 (95% CI 1.07–1.66) respectively. No association was observed between gastroenteritis and the subsequent risk of prescription medication for arthritis (p=0.49).
Conclusions
Acute bacterial gastroenteritis necessitating medical attention was associated with a higher risk of arthritic symptoms, but not arthritic medications, up to four years later. The nature and chronicity of these arthritic symptoms requires further study.
doi:10.1093/rheumatology/kem339
PMCID: PMC2876134  PMID: 18184664 CAMSID: cams965
Health survey; Cohort study; Escherichia coli O157; Campylobacter; Environmental exposure; Arthritis
16.  Time use patterns among women with rheumatoid arthritis: association with functional limitations and psychological status 
Rheumatology (Oxford, England)  2006;46(3):490-495.
Objectives
. This study assessed time use patterns among 375 women with rheumatoid arthritis (RA). We hypothesized that (i) as functional limitations increased, time use imbalances would occur (i.e. time needed for obligatory activities would conflict with time needed for productive and free-time activities) and (ii) time use imbalances would be associated with psychological distress.
Methods
. Time use estimates were obtained from written questionnaires; other study data were collected from annual telephone interviews. Activities were categorized as obligatory, committed or discretionary, as defined by Verbrugge. Time use estimates were aggregated to define number of obligatory (e.g. self-care) activities requiring >2 h/day and a number of committed and discretionary activities in which no time was spent each day.
Results
. After adjusting for age, education, marital status and pain severity, women with more functional limitations were significantly more likely to spend >2 h/day in obligatory activities. As functional limitations increased, the proportion spending no time in each committed activity and many discretionary activities increased. Spending >2 h/day in obligatory activities was not significantly associated with poor psychological status, but spending no time in a greater number of committed and discretionary activities was associated with lower life satisfaction and higher levels of depressive symptoms.
Conclusions
. Having more severe functional limitations appears to shift time use patterns towards more time spent in obligatory activities and less time spent in committed and discretionary activities. These imbalances in time use were associated with psychological distress, highlighting the need for women with RA to maintain important productive, social and discretionary activities.
doi:10.1093/rheumatology/kel299
PMCID: PMC2875174  PMID: 16936332
Rheumatoid arthritis (RA); Disability; Functioning; Psychological well-being; Time use
17.  Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis 
Rheumatology (Oxford, England)  2008;48(2):134-139.
Objective. To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis.
Methods. Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses.
Results. A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P ≤ 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically.
Conclusions. Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.
doi:10.1093/rheumatology/ken441
PMCID: PMC2634286  PMID: 19074186
Myositis; Manual muscle test; Strength; Rehabilitation
18.  Distribution and Severity of Weakness Among Patients with Polymyositis, Dermatomyositis and Juvenile Dermatomyositis 
Rheumatology (Oxford, England)  2008;48(2):134-139.
Objective
To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with polymyositis (PM), dermatomyositis (DM) and juvenile dermatomyositis (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis.
Methods
Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes such as clinical course, muscle enzymes, corticosteroid dosage, and functional status were evaluated for association with strength using univariate and multivariate analyses.
Results
A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (p ≤ 0.05). Hip flexors, hip extensors, hip abductors, neck flexors, and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically.
Conclusions
Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison to DM.
doi:10.1093/rheumatology/ken441
PMCID: PMC2634286  PMID: 19074186
Myositis; manual muscle test; strength; rehabilitation
20.  The Cutaneous Assessment Tool (CAT): Development and Reliability in Juvenile Idiopathic Inflammatory Myopathy 
Rheumatology (Oxford, England)  2007;46(10):1606-1611.
Objectives
Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients.
Methods
The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty three children were assessed by 11 pediatric rheumatologists at ten centers. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC).
Results
Simple agreements in recognizing lesions as present or absent were generally high (0.5 – 1.0). ICC's for CAT lesions were moderate (0.4 – 0.75) in both slides and real patients. ICC's for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 – 44 (median 7, potential range 0 – 96) and CAT damage scores ranged from 0 – 13 (median 1, potential range 0 – 22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%).
Conclusions
Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM.
doi:10.1093/rheumatology/kem179
PMCID: PMC2598780  PMID: 17890275
Juvenile Idiopathic Inflammatory Myopathy; Juvenile Dermatomyositis; Skin Disease; Cutaneous Assessment Tool; CAT; Assessment
21.  Heart failure among younger rheumatoid arthritis and Crohn’s patients exposed to TNF-α antagonists 
Rheumatology (Oxford, England)  2007;46(11):1688-1693.
Objectives
New onset heart failure (HF) has been associated with the use of TNF-α antagonists etanercept and infliximab based upon spontaneous adverse event reports. HF clinical trials of these agents were stopped early due to futility or worsening of existing HF. A potential association between etanercept and infliximab and new onset HF has been studied minimally at a population level.
Methods
Using administrative claims from a large U.S. health care organization, we identified rheumatoid arthritis (RA) and Crohn’s disease (CD) patients receiving infliximab or etanercept (exposed), and comparator cohorts of RA and CD patients receiving non-biologic immunosuppressives (unexposed). We studied adults <50 years to reduce potential confounding related to common age-related comorbidities. Based on abstracted medical records of suspected HF cases, a physician panel adjudicated cases as definite, possible or no HF.
Results
Among 4018 RA and CD patients with mean duration follow-up of 18 months, 9 of 33 suspected HF cases (identified using claims data) were adjudicated as definite (n = 5) or possible (n = 4) HF. The relative risk of HF among TNF-α antagonist-treated RA and CD patients was 4.3 and 1.2, respectively (P = NS for both). The absolute difference in cumulative incidence of HF among infliximab or etanercept-exposed compared to unexposed patients was 3.4 and 0.3 cases per 1000 persons for RA and CD (P = NS), respectively, yielding a number needed to harm of 294 for RA and 3333 for CD.
Conclusion
We found only a small number of presumed HF cases (n = 9, or 0.2%) in a large population of relatively young RA and CD patients. Although there was an increased relative risk of incident, HF that was not statistically significant among those exposed to TNF-α antagonists compared to those unexposed, larger cohorts are needed to provide more precise risk estimates and permit adjustment for potential confounding.
doi:10.1093/rheumatology/kem212
PMCID: PMC2442887  PMID: 17938138
Heart failure; rheumatoid arthritis; Crohn’s disease; infliximab; etanercept; TNF-α antagonists; adverse events
22.  Are Rheumatologists’ Treatment Decisions Influenced by Patients’ Age? 
Rheumatology (Oxford, England)  2006;45(12):1555-1557.
Purpose
The objective of this study was to determine whether physicians’ treatment preferences are influenced by patients’ age.
Methods
We mailed a survey to a random sample of rheumatologists practicing in the U.S. The survey included a scenario describing a hypothetical patient with rheumatoid arthritis (RA) on hydroxychloroquine, sulfasalazine, and low dose prednisone, who presents with active disease during a follow-up appointment. The scenario was formulated in two versions which were identical except for the age of the patient. After reading the scenario, respondents were asked to rate (on a 10 cm numerical rating scale) their recommendations for each of the three options: 1) increasing the dose of prednisone, 2) adding a new disease modifying anti-rheumatic drug (DMARD), and 3) switching DMARDs. Rheumatologists who rated either adding a new DMARD or switching DMARDs higher than increasing the dose of prednisone were classified as “preferring aggressive treatment with DMARDs”, while the remaining rheumatologists were classified as “NOT preferring aggressive treatment with DMARDs”.
Results
480 rheumatologists were mailed a questionnaire; 204 responded for a response rate of 42.5%. Overall 163 (80%) of respondents were classified as preferring aggressive treatment with DMARDs. Rheumatologists responding to this survey were more likely to prefer aggressive DMARD treatment for the young RA patient versus the older RA patient (87% versus 71%, p=0.007).
Conclusions
Our findings suggest that rheumatologists’ treatment recommendations may be influenced by age. Future educational efforts should increase physician awareness of this possible bias in order to ensure equal service delivery across ages.
doi:10.1093/rheumatology/kel144
PMCID: PMC1660557  PMID: 16690762
Rheumatoid Arthritis; Disease Modifying Anti-Rheumatic Drugs; Decision-making
23.  SNPs in the FOXP3 gene region show no association with Juvenile Idiopathic Arthritis in a UK Caucasian population 
Rheumatology (Oxford, England)  2007;46(8):1263-1265.
Objective
A region on the short arm of the X-chromosome, Xp11, has previously been linked to childhood-onset polyarthritis. Mapping to the linked region is FOXP3, a transcription factor that regulates regulatory T cell (Treg) development and function. The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the FOXP3 gene region contribute to JIA susceptibility.
Method
Nine FOXP3 SNPs were genotyped in 761 JIA cases and 402 controls using the Sequenom® MassARRAY® system. Association was measured using either χ2 or Fisher's exact test at the allelic and genotypic level. Furthermore, cases and controls were stratified by gender and association measured for each stratum.
Results
None of the SNPs showed an association with JIA. Similarly, the lack of association was also evident in both the female and male cohorts.
Conclusion
Although FOXP3 presents itself as a good candidate for contributing to JIA susceptibility, this study, which was powered to detect associations with genotypic relative risk >2 in the female cohort, has failed to find an association between SNPs in the FOXP3 gene region and JIA.
doi:10.1093/rheumatology/kem129
PMCID: PMC1955685  PMID: 17526924
FOXP3; Juvenile idiopathic arthritis; Association analysis; X-linked gene

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