Treat to Target guidelines promote shared decision-making (SDM) in rheumatoid arthritis (RA). Also, due to high cost and potential toxicity of therapies, SDM is central to patient safety. Our objective was to examine patterns of perceived communication around decision-making in two cohorts of adults with RA.
Data were derived from patients enrolled in one of two longitudinal, observational cohorts (UCSF RA Cohort and RA Panel). Subjects completed a telephone interview in their preferred language that included a measure of patient-provider communication, including items about decision-making. Measures of trust in physician, education, and language proficiency were also asked. Logistic regression was performed to identify correlates of suboptimal SDM communication. Analyses were performed on each sample separately.
Of 509 patients across two cohorts, 30% and 32% reported suboptimal SDM communication. Low trust in physician was independently associated with suboptimal SDM communication in both cohorts. Older age and limited English proficiency were independently associated with suboptimal SDM in the UCSF RA Cohort, as was limited health literacy in the RA Panel.
This study of over 500 adults with RA from two demographically distinct cohorts found that nearly one-third of subjects report suboptimal SDM communication with their clinicians, regardless of cohort. Lower trust in physician was independently associated with suboptimal SDM communication in both cohorts, as was limited English language proficiency and older age in the UCSF RA Cohort and limited health literacy in the Panel. These findings underscore the need to examine the impact of SDM on health outcomes in RA.
arthritis; rheumatoid; health communication; health literacy; trust
The most rapidly growing population of patients undergoing total knee arthroplasty (TKA) is under the age of 65. The objective of this study was to gain insight into the factors influencing physicians’ recommendations for persons in this age group with moderate osteoarthritis (OA).
Rheumatologists and orthopedic surgeons attending national meetings were asked to complete a survey including a standardized scenario of a 62 year old person with knee OA who has moderate knee pain limiting strenuous activity despite medical management. We used an experimental 2×2×2 design to examine the effects of gender, employment status and severity of radiographic OA on physicians’ recommendations. Each physician was asked to rate a single scenario.
The percent of physicians recommending TKA varied from 30% to 55% for scenarios describing a patient with mild radiographic OA, and from 39% to 71% for scenarios describing a patient with moderate radiographic OA. Surgeons were less likely to recommend TKA for women compared to men of the same age, employment status, symptom severity and functional status, and x-rays. Rheumatologists practicing in academic settings were more likely to recommend TKA compared to those practicing in non-academic settings, and American surgeons were more likely to recommend TKA compared to their European counterparts.
Orthopedic surgeons and rheumatologists vary significantly in their recommendations for patients with moderate knee pain and functional limitations. Both patient and physician characteristics influence physicians’ recommendations and rheumatologists and orthopedic surgeons display different patterns of decision-making.
Total Joint Arthroplasty; Practice Patterns; Physician Bias; Unwarranted Variability
Poor functional outcomes post knee replacement are common, but
estimates of its prevalence vary, likely in part because of differences in
methods used to assess function. The agreement between improvement in
function and absolute good levels of function after knee replacement has not
been evaluated. We evaluated the attainment of improvement in function and
absolute good function after total knee replacement (TKR) and the agreement
between these measures.
Using data from The Multicenter Osteoarthritis (MOST) Study, we
determined the prevalence of achieving a minimal clinically important
improvement (MCII, ≥ 14.2/68 point improvement) and Patient
Acceptable Symptom State (PASS, ≤ 22/68 post-TKR score) on the
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
Physical Function subscale at least 6 months after knee replacement. We also
assessed the frequency of co-occurrence of the 2 outcomes, and the
prevalence according to pre-knee replacement functional status.
We included 228 subjects who had a knee replacement during followup
(mean age 65 yrs, mean body mass index 33.4,73% female). Seventy-one
percent attained the PASS for function after knee replacement, while only
44% attained the MCII. Of the subjects who met the MCII, 93%
also attained the PASS; however, of subjects who did not meet the MCII,
54% still achieved a PASS. Baseline functional status was associated
with attainment of each MCII and PASS.
There was only partial overlap between attainment of a good level of
function and actually improving by an acceptable amount. Subjects were more
likely to attain an acceptable level of function than to achieve a
clinically important amount of improvement post knee replacement.
To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA).
We conducted a prospective study consisting of 662 RA patients followed up to 7 years from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured by the Disease Activity Score examined in 28 commonly affected joints (DAS28-CRP3) and Modified Health Assessment Questionnaire (MHAQ) assessed annually. Linear mixed models were developed to assess the longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE) by smoking and alcohol interactions were also evaluated in the analysis.
The median follow-up time of the cohort was 4 years. Current smoking was not associated with DAS28-CRP3 in this study, but was associated with a higher MHAQ than non-smokers in seropositive RA (p=0.05). Alcohol consumption showed an approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1–10.0 grams/day. Compared to no alcohol use, alcohol consumption of 5.1–10.0 grams/day was associated with a significant decrease of MHAQ (P=0.02). When stratified by HLA-SE, the effect of alcohol consumption appeared to be stronger in HLA-SE positive RA than HLA-SE negative RA.
We found that current smoking was associated with a worse functional status, while moderate alcohol consumption was associated with a better functional status in RA. Replications of these findings in other prospective studies are needed.
Smoking; Alcohol Consumption; Rheumatoid Arthritis; HLA Shared Epitope; DAS28; MHAQ; Gene-Environment Interaction
To perform a systematic review of 30- and 90-day mortality rates in patients undergoing hip or knee arthroplasties.
Five databases were searched for English-language studies of mortality in hip or knee arthroplasties and the following data were extracted: patient characteristics (age, gender, ethnicity), arthroplasty characteristics (unilateral vs bilateral, hip vs knee), system factors (hospital volume and surgeon volume), year of study, etc… Mortality rates were compared across variable categories; proportions were compared using relative risk ratios and 95% confidence intervals.
Out of 650 titles and abstracts, 80 studies qualified for data inclusion. 35%, 34% and 31% studies provided 30-, 90- and >90-day mortality rates. Overall 30-day mortality rates published across all types of arthroplasties were 0.3%, 90-day: 0.7%. For those reports with specific rates, 30-day mortality was significantly higher in men than women (1.8% vs 0.4%; relative risk (RR): 3.93, 95% confidence interval (CI), 3.30–4.68) and bilateral vs unilateral procedures (0.5% vs 0.3%; RR, 1.6, 95% CI:1.49–1.72), but no differences were noted by the underlying diagnosis of osteoarthritis vs rheumatoid arthritis (0.4% vs 0.3%; RR 0.77, 95% CI:0.48–1.24). 90-day mortality showed non-significant trends favoring women, osteoarthritis as the underlying diagnosis, and unilateral procedures.
Several demographic and surgical factors were associated with higher 30-day mortality rates following knee and hip arthroplasties. More studies are needed to examine the effect of body mass index, comorbidities, and other modifiable factors, in order to identify interventions designed to lower mortality rates following arthroplasty procedures.
Mortality; Total Knee Arthroplasty; Total Hip Arthroplasty; Short-term mortality
To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and Non-Hispanic White (NHW) children.
There were 3,967 NHW and AA children with JIA enrolled in the CARRA Registry. Demographic and disease-related data were collected from time of diagnosis to enrollment. Children with JIA alone were compared to those with JIA-U. Children with JIA-U were then compared by race.
Mean age of children with JIA-U was 11.4 years (±4.5), 76.9% were female and 2.8% were AA. Children with JIA-U were younger at arthritis onset, female, required more medications, had <5 joints involved, had oligoarticular JIA, and ANA (+), RF (−) and anti-CCP (−). AA children with JIA-U had decreased uveitis frequency, were older at arthritis onset and more frequently diagnosed with enthesitis-related JIA. Predictors of uveitis development include female gender, early age of arthritis onset, and oligoarticular persistent and extended JIA classification, whereas polyarticular RF-positive JIA was protective.
The prevalence of JIA-U in AA and NHW children is 11.6% in the CARRA registry. Known risk markers (ANA, age at arthritis onset, and oligoarticular JIA) were more frequent in our JIA-U cohort. AA children had a lower frequency of JIA-U. There were significant differences in age of arthritis onset and JIA subtype between NHW and AA children, although the ANA, RF and HLA-B27 were similar. Exploration of race as a risk factor should be considered.
juvenile idiopathic arthritis; uveitis; risk markers; outcomes
The OMERACT Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges due to their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment.
A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient or disease centred-variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondyloarthritis and knee osteoarthritis were then evaluated using the original OMERACT filter and the newly proposed structure. Break-out groups critically reviewed the extent to which the candidate biomarkers complied with the proposed step-wise approach, as a way of examining the utility of the proposed 3 dimensional structure.
Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials.
General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0.
biomarkers; imaging; OMERACT filter; validation framework
The OMERACT Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The ‘Truth’ section of the OMERACT Filter pre-supposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement (“Filter 2.0 Core Areas of Measurement”) was presented at OMERACT 11 to explore areas of consensus and consider whether already endorsed core outcome sets fit in to this newly proposed framework.
Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved.
Although there was a broad acceptance of the framework in general, several important areas of construction, presentation and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues.
These issues will require resolution in order to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials.
Five core domains have been endorsed by Outcomes Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. The aim of this work was to evaluate instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination.
A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by two reviewers to summarise information according to the specific components of the OMERACT filter.
Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point patient global assessment of response to treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain.
Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.
gout; pain; measurement; outcome
Hypertension, a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with hypertension in RA.
We compared measures of inflammation (serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), homocysteine and leptin concentrations) and insulin resistance (homeostasis model assessment index (HOMA)) in RA patients with (n=90) and without hypertension (n=79). Hypertension was defined as blood pressure ≥140/90 mmHg or treatment with antihypertensive therapy. The independent association of markers of interest with hypertension was examined using multivariable logistic regression.
Hypertensive patients were significantly older and had longer disease duration than those without hypertension (both P<0.001). Concentrations of homocysteine (11.1[8.5–13.5] μmol/L vs. 9.3[7.8–11.0] μmol/L were significantly higher in hypertensive patients (P<0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and NSAID use, increased concentrations of homocysteine (OR 2.9, 95%CI: 1.5–5.5, P=0.001), and leptin (OR 2.0, 95%CI: 1.0–3.8, P=0.046) were significantly associated with hypertension, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α and HOMA index were not (all P values >0.05).
Hypertension in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of hypertension in RA may involve pathways more likely usually associated with fat and vascular homeostasis.
rheumatoid arthritis; inflammation; hypertension; blood pressure; homocysteine; leptin; insulin resistance
Patients with systemic lupus erythematosus (SLE) are at increased risk of herpes zoster (HZ). Although a vaccine for HZ has been FDA approved, its use in immunocompromised individuals remains controversial because it is a live-attenuated virus vaccine. We performed a pilot study of the immunogenicity of Zostavax® in SLE patients.
Ten SLE patients and 10 controls ≥50 years old participated in this open label vaccination study. All were seropositive for varicella zoster virus (VZV). SLE patients were excluded for SLEDAI>4, use of mycophenolatemofetil, cyclophosphamide, biologics, or >10 mg prednisone daily. Follow-up visits occurred at 2, 6, and 12 weeks. Clinical outcomes included the development of adverse events, particularly HZ or vesicular lesions, and SLE flare. Immunogenicity was assessed with VZV-specific IFN-γ producing ELISPOT assays and with antibody concentrations.
All subjects were women. SLE patients were slightly older than controls (60.5 vs. 55.3 years, p<0.05) Median baseline SLEDAI was 0 (range 0–2) for SLE patients. No episodes of HZ, vesicular rash, serious adverse events, or SLE flares occurred. Three injection site reactions occurred in each group: mild erythema or tenderness. The proportion of subjects with a >50% increase in ELISPOT results following vaccination was comparable between both groups, although absolute SLE responses were lower than controls. Antibody titers increased only among controls following vaccination (p<0.05).
Zostavax vaccination yielded a measurable immuneresponse in this cohort of mild SLE patients on mild-moderate immunosuppressive medications. No herpetiform lesions or lupus flares were seen in this small cohort of patients.
Systemic lupus erythematosus; herpes zoster; vaccine; Zostavax; infection; clinical trial
The OMERACT Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The ‘Truth’ section of the OMERACT Filter requires that criteria be met to demonstrate that the outcome instrument meets the criteria for content, face and construct validity.
Discussion groups critically reviewed the variety of ways in which case studies of current OMERACT Working Groups complied with the ‘Truth’ component of the Filter and what issues remained to be resolved.
The case studies showed that there is broad agreement on criteria for meeting the ‘Truth’ criteria through demonstration of content, face and construct validity; however several issues were identified that the Filter Working Group will need to address.
These issues will require resolution in order to reach consensus on how ‘Truth’ will be assessed for the proposed Filter 2.0 framework, for instruments to be endorsed by OMERACT.
To determine the extent to which instruments that measure core outcome domains in acute gout fulfil the OMERACT filter requirements of truth, discrimination and feasibility.
Patient-level data from four randomised controlled trials of agents designed to treat acute gout and one observational study of acute gout were analysed. For each available measure construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic and repeated measures generalised estimating equations were assessed. Floor and ceiling effects were also assessed and MCID was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement.
There was evidence for construct validity and discriminative ability for 3 measures of pain (0 to 4 Likert, 0 to 10 numeric rating scale, 0 to 100 mm visual analogue scale). Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment.
There is sufficient evidence to support measures of pain (using Likert, numeric rating scale or visual analogue scales), joint tenderness and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.
gout; outcome measures; psychometrics
To evaluate routinely collected non-invasive tests from two systemic sclerosis (SSc) cohorts to determine their predictive value alone and in combination vs. right heart catheterization (RHC)- confirmed pulmonary arterial hypertension (PAH).
We evaluated two cohorts of patients who were at risk or with incident PAH: (1) The Pulmonary Hypertension Assessment and Recognition Outcomes in Scleroderma (PHAROS) cohort and (2) an inception SSc cohort at Cochin Hospital. Estimated right ventricular systolic pressure (eRVSP) on echocardiogram (TTE) and and pulmonary function tests (PFT) parameters were evaluated and their predictive values determined. We then evaluated patients with PAH missed on TTE cutoffs that were subsequently identified by a PFT parameter.
In the PHAROS cohort (N=206), 59 (29%) had RHC-defined PAH. An eRVSP threshold of 35–50mmHg failed to diagnose PAH in 7–31% of patients, 50–70% of which (N=2–13) were captured by PFT parameters. In the Cochin cohort (N=141), 10 (7%) patients had RHC confirmed PAH. An eRVSP threshold of 35–50mmHg missed 0–70% (N = 0–7) patients, of which 0–68% (N = 0–6) were captured by PFT parameters. The combination of TTE and PFT improved the negative predictive value for diagnosing PAH.
In 2 large SSc cohorts, screening with TTE and PFT captured majority of patients with PAH. TTE and PFT complement each other for the diagnosis of PAH.
Echocardiogram; Pulmonary Function Tests; Screening; Diagnosis; Systemic Sclerosis; Pulmonary Hypertension; Pulmonary Arterial Hypertension
Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA, and whether such risk occurs early following disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.
We studied a population-based inception cohort with RA from Olmsted County, Minnesota. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.
The hazard ratio (HR) [95% CI] for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 [1.36–1.96] for women and 1.40 [1.02–1.93] for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years (HR: 1.43 [1.16–1.77] and 1.34 [0.92–1.94], respectively), or at age < 50 years (HR: 2.34 [1.61–3.42] and 1.74 [0.91–3.30], respectively). However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR: 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).
Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.
rheumatoid arthritis; bone fractures; osteoporosis; epidemiology
To determine the diagnostic test performance of location of pain and activity-related pain in identifying knees with patellofemoral joint (PFJ) structural damage.
The Multicenter Osteoarthritis Study is a US National Institutes of Health-funded cohort study of older adults with or at risk of knee osteoarthritis. Subjects identified painful areas around the knee on a knee pain map and the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain with stairs and walking on level ground. Cartilage damage and bone marrow lesions were assessed from knee magnetic resonance imaging. We determined the sensitivity, specificity, positive and negative predictive values for presence of anterior knee pain (AKP), pain with stairs, absence of pain while walking on level ground, and combinations of tests in discriminating knees with isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ) or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our analyses because of the inability to determine which compartment was causing pain.
There were 407 knees that met our inclusion criteria. “Any” AKP had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of moderate pain with walking on level ground had the greatest sensitivity (93%) but poor specificity (13%). The combination of “isolated” AKP and moderate pain with stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies tested.
Commonly used questions purported to identify knees with PFJ structural damage do not identify this condition with great accuracy.
OSTEOARTHRITIS; PAIN; MAGNETIC RESONANCE IMAGING
Gout; gouty arthritis; research priorities; patient; nominal group; NGT; diet; supplements
To determine the extent to which OMERACT participants agree that instruments that have been used in clinical trials and measure OMERACT core outcome domains in acute gout fulfil the filter requirements of truth, discrimination and feasibility and to determine where future research efforts need to be directed.
The results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted ‘don’t know’).
The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or VAS (0 to 100mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed.
Measures of pain, joint swelling, joint tenderness and patient global assessment in acute gout were endorsed at OMERACT-11. These measures should now be used in clinical trials of acute gout.
gout; outcome measures; psychometrics
The objective of this study was to determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives of rheumatoid arthritis (RA) patients in two indigenous North American populations with high prevalence of RA.
Participants were recruited from two indigenous populations in Canada and the United States, including RA patients (probands), their unaffected first-degree relatives, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared epitope alleles present.
Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p <0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p=0.0082) and anti-CCP antibodies (p=0.008), but not smoking or shared epitope alleles.
Despite a significant prevalence of anti-CCP in first-degree relatives, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration and anti-CCP in RA.
Arthritis; Rheumatoid; Autoantibodies; peptidylarginine deiminase
To evaluate the outcome of TNF-alpha inhibition (anti-TNFα) for pediatric uveitis.
We retrospectively assessed children (≤18 years) with non-infectious uveitis receiving anti-TNFα at five uveitis centers and one pediatric-rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥2 consecutive ophthalmological exams ≥28 days apart while taking no oral and ≤2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses.
Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% confidence interval [95% CI]: 62–87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI: 51–76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype amongst JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75–80% lower rate of achieving quiescence under anti-TNFα - independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis re-activated within 12 months of achieving quiescence in 14% of those continuing anti-TNFα (95% CI: 6–31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI: 1–43%).
Treatment with anti-TNFα was successful and sustained in a majority of children with non-infectious uveitis and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNFα.
uveitis; tumor necrosis factor-alpha antagonist; juvenile idiopathic arthritis
To evaluate the content and construct validity of an individualized patient-reported instrument, the Patient-generated Index (PGI), in patients with systemic sclerosis (SSc), and to compare its performance to that of other instruments and to the Patient-reported Outcomes Measurement Information System (PROMIS) framework.
Patients identified the 5 most important life areas affected by SSc, which we categorized into domains of the PROMIS framework (mental, physical, and social). Correlations were obtained between PGI and the Health Assessment Questionnaire (HAQ), the Medical Outcomes Study Short Form-36 (SF-36), and the Symptom Burden Index (SBI) scores.
Sixty-two patients with SSc completed the PGI: 87% women, 69% white, mean age 53 years, mean disease duration 8 years, and 63% with diffuse disease. A total of 258 individual life area responses were recorded: 54% in social health (social function and relationship subcomponents); 28% in physical health (physical function, symptoms, general physical health); and 19% in mental health (consisting largely of the affect subcomponent). Patient PGI responses were categorized into 6 of the 7 subcomponents of the PROMIS framework; substance use/alcohol was not identified. Statistically significant correlations ranging in absolute value from 0.26 to 0.50 were observed between the PGI and the HAQ, SF-36 summary component scores, and the large majority of SF-36 subscales and SBI components.
The PGI is a personalized instrument that adequately assessed a wide range of health-related quality of life outcomes within the PROMIS framework. The PGI captured additional constructs not yet defined within the framework that are important for patients with SSc.
SCLERODERMA; PATIENT-GENERATED INDEX; PATIENT-CENTERED OUTCOMES; SYSTEMIC SCLEROSIS
The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients.
Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantitate lung volume and parenchymal density.
Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging was free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density.
Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with two characteristic physiological abnormalities: 1) impaired respiratory force at high but not low lung volumes, and 2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example via neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.
Shrinking Lung Syndrome; Pleuritis; Pleurisy; Systemic Lupus Erythematosus; Lung