Syndesmophyte Growth in Ankylosing Spondylitis: from Laboratory to Bedside.

PURPOSE OF REVIEW: This study aims to review recent studies on risk factors for syndesmophyte growth in ankylosing spondylitis (AS) and on treatment effects. RECENT FINDINGS: New genetic studies, including a genome-wide association study, provided only limited evidence of specific genetic associations with radiographic severity. Measures of inflammation, including vertebral osteitis and C-reactive protein level, were strongly associated with radiographic progression, while studies of adipokines had mixed results. Mesenchymal stem cells from HLA-B27 positive AS patients were found to promote vertebral ossification via a pathway of B27 misfolding, retinoic acid receptor-ß activation, and increased bone alkaline phosphatase. Low vertebral trabecular bone density is associated with syndesmophyte growth, with reciprocal effects when bridged. Several observational studies suggested radiographic severity was reduced by treatment with tumor necrosis factor inhibitors, particularly when longer than 2 years. Syndesmophyte development in AS is the result of a complex, incompletely understood, interplay of inflammatory and mechanical factors.

EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). METHODS: Following European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion. RESULTS: Four overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering. CONCLUSION: These recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

OBJECTIVE: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. METHODS: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. RESULTS: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. CONCLUSIONS: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Corticosteroid discontinuation, complete clinical response and remission in juvenile dermatomyositis.

OBJECTIVE: A North American registry of JDM patients was examined for frequency of and factors associated with corticosteroid discontinuation, complete clinical response and remission. METHODS: We evaluated probability of achieving final corticosteroid discontinuation, complete clinical response and remission in 307 JDM patients by Weibull time-to-event modelling; conditional probability of complete clinical response and remission using Bayesian network modelling; and significant predictors with multivariable Markov chain Monte-Carlo Weibull extension models. RESULTS: The probability of corticosteroid discontinuation was 56%, complete clinical response 38% and remission 30% by 60 months after initial treatment in 105 patients. The probability of remission was conditional on corticosteroid discontinuation and complete clinical response. Photosensitivity, contractures and a longer time to complete clinical response were predictive of the time to final corticosteroid discontinuation. Anti-MJ (NXP2) autoantibodies and a Northwest residential geoclimatic zone were predictive of shorter time to complete clinical response, while dysphonia, contractures, an increase in medications within 24 months and a longer time to corticosteroid discontinuation were associated with longer time to complete clinical response. Anti-p155/140 (TIF1) autoantibodies, an increase in medications within 12-24 months, or longer times to corticosteroid discontinuation and complete clinical response were associated with longer time to remission. CONCLUSION: JDM patients achieve favourable outcomes, including corticosteroid discontinuation, complete clinical response and remission, although timelines for these may be several years based on time-dependent analyses. These outcomes are inter-related and strong predictors of each other. Selected clinical features and myositis autoantibodies are additionally associated with these outcomes.

Accuracy of diagnoses of inflammatory arthritis in administrative hospitalization databases.

PURPOSE: Studies using administrative hospitalization data often classify patients as having inflammatory arthritis based on diagnoses recorded at the hospitalization. We examined the agreement of these diagnoses with patients' prior medical histories. METHODS: We identified Medicare beneficiaries hospitalized in 2011 to 2015 for total hip arthroplasty (THA), total knee arthroplasty (TKA), acute myocardial infarction (AMI), or sepsis. We compared diagnoses of rheumatoid arthritis (RA) or ankylosing spondylitis (AS) at the index hospitalization to diagnoses over prior inpatient and outpatient claims. To assess the impact of potential misclassification, we compared hospital outcomes using the alternative methods of detecting beneficiaries with arthritis. Analyses were repeated using Medicaid data. RESULTS: Among 506 781 Medicare beneficiaries with THA, 18282 had RA and 571 had AS at the arthroplasty hospitalization, while 13 212 had RA and 1519 had AS based on claims history. Diagnoses at the hospitalization were highly specific (0.98-0.99), but sensitivities (0.65 for RA; 0.31 for AS) and positive predictive values (PPV) (0.47 for RA; 0.83 for AS) were lower. For TKA, AMI, and sepsis, specificities were 0.97 to 0.99, sensitivities 0.60 to 0.66 for RA and 0.18 to 0.22 for AS, and PPVs 0.43 to 0.47 for RA and 0.73 to 0.77 for AS. In Medicaid, sensitivities were 0.21 to 0.67 for RA and 0.07 to 0.49 for AS. Frequencies of some hospital outcomes differed when arthritis was classified by the index hospitalization or claims history. CONCLUSION: Diagnoses of RA and AS in hospitalization databases are highly specific but fail to identify large proportions of patients with these diagnoses.

Racial/Ethnic Differences in Dialysis Discontinuation and Survival after Hospitalization for Serious Conditions among Patients on Maintenance Dialysis.

BACKGROUND: Racial and ethnic minorities on dialysis survive longer than whites, and are less likely to discontinue dialysis. Both differences have been attributed by some clinicians to better health among minorities on dialysis. METHODS: To test if racial and ethnic differences in dialysis discontinuation reflected better health, we conducted a retrospective cohort study of survival and dialysis discontinuation among patients on maintenance dialysis in the US Renal Data System after hospitalization for either stroke (n=60,734), lung cancer (n=4100), dementia (n=40,084), or failure to thrive (n=42,950) between 2003 and 2014. We examined the frequency of discontinuation of dialysis and used simulations to estimate survival in minorities relative to whites if minorities had the same pattern of dialysis discontinuation as whites. RESULTS: Blacks, Hispanics, and Asians had substantially lower frequencies of dialysis discontinuation than whites in each hospitalization cohort. Observed risks of mortality were also lower for blacks, Hispanics, and Asians. In simulations that assigned discontinuation patterns similar to those found among whites across racial and ethnic groups, differences in survival were markedly attenuated and hazard ratios approached 1.0. Survival and dialysis discontinuation frequencies among American Indians and Alaska Natives were close to those of whites. CONCLUSIONS: Racial and ethnic differences in dialysis discontinuation were present among patients hospitalized with similar health events. Among these patients, survival differences between racial and ethnic minorities and whites were largely attributable to differences in the frequency of discontinuation of dialysis.

Chronic oral anticoagluation and risk of prostate cancer: Evidence of detection bias.

Warfarin treatment has been associated with lower risks of prostate cancer, without a specified biological mechanism. Our study tested the hypothesis that reluctance to perform prostate biopsies in men who are anticoagulated results in lower rates of diagnosed prostate cancer, leading to an apparent protective effect. Rates of prostate biopsies have decreased from 2000 to 2015, allowing calendar time to be used as the intervention. In a national population-based sample of elderly men, our study compared trends in prostate cancer incidence between 17,815 men treated with chronic oral anticoagulation for prosthetic heart valve thromboprophylaxis and a general population comparison group of 356,300 men. Cancer events were based on administrative claims. Among men enrolled in 2000-2001 and followed through 2015, prostate cancer incidence was substantially lower in the anticoagulation group (adjusted incidence rate ratio [IRR] 0.70; 95% confidence interval [CI] 0.62-0.80). Incidence decreased over time in the general population group to approach that of the anticoagulation group among men enrolled in 2008-2010 (IRR 0.86; 95% CI 0.71-1.04). Rates of prostate biopsies also decreased over time in the general population group to match the rate in the anticoagulation group. These results indicate that the apparent protective effect of warfarin treatment on the risk of prostate cancer is likely the result of detection bias from lower rates of biopsies among men who are anticoagulated.

Pre-operative withholding of infliximab and the risk of infections after major surgery in patients with rheumatoid arthritis.

OBJECTIVES: Withholding TNF inhibitors (TNFI) before surgery has been recommended due to concern for post-operative infection. We examined the risks of post-operative infections and mortality in patients with RA in relation to the pre-operative timing of infliximab infusion. METHODS: In this population-based retrospective cohort study, we used US Medicare claims data from 2007 to 2015 to identify patients with RA who underwent coronary artery bypass grafting (CABG), aortic or vascular surgery, or bowel resection, and who were treated with infliximab in the 90 days prior to surgery. We examined associations between the timing of infusion and infections and mortality in the 30 days after surgery. We adjusted for the predicted probability of post-operative infection or death, demographic characteristics, use of MTX, post-operative blood transfusion and hospital volume. RESULTS: We studied 712 patients with CABG, 244 patients with vascular surgery and 862 patients with bowel resections. Post-operative pneumonia occurred in 7.4-11.9%, urinary tract infection in 9.0-15.2%, surgical site infection in 3.2-18.9%, sepsis in 4.2-9.6% and death in 3.5-7.0% among surgery cohorts. There was no association between the time from last infliximab dose to surgery and the risk of post-operative infection or mortality in any surgical cohort. No subgroups were identified that had an increased risk of infection with more proximate use of infliximab. CONCLUSION: Among elderly patients with RA, risks of infection and mortality after major surgery were not related to the pre-operative timing of infliximab infusion.

Risks of solid cancers in elderly persons with osteoarthritis or ankylosing spondylitis.

OBJECTIVES: Patients with osteoarthritis and ankylosing spondylitis have lower cancer-related mortality than the general population. We examined risks of solid cancers at 16 sites in elderly patients with knee or hip osteoarthritis (KHOA) or ankylosing spondylitis. METHODS: In this population-based retrospective cohort study, we used US Medicare data from 1999 to 2010 to identify cohorts of persons with KHOA or ankylosing spondylitis, and a general population group without either condition, who were followed through 2015. We compared cancer incidence among groups, adjusted for age, sex, race, socioeconomic characteristics, geographic region, smoking and comorbidities. RESULTS: We studied 2 701 782 beneficiaries with KHOA, 13 044 beneficiaries with ankylosing spondylitis, and 10 859 304 beneficiaries in the general population group. Beneficiaries with KHOA had lower risks of cancer of the oropharynx, oesophagus, stomach, colon/rectum, hepatobiliary tract, pancreas, larynx, lung, and ovary than the general population. However, beneficiaries with KHOA had higher risks of melanoma, renal cell cancer, and cancer of the bladder, breast, uterus and prostate. Associations were similar in ankylosing spondylitis, with lower risks of cancer of the oesophagus, stomach, and lung, and higher risks of melanoma, renal cell cancer, and cancer of the renal pelvis/ureter, bladder, breast, and prostate. CONCLUSION: Lower risks of highly prevalent cancers, including colorectal and lung cancer, may explain lower cancer-related mortality in patients with KHOA or ankylosing spondylitis. Similarities in cancer risks between KHOA and AS implicate a common risk factor, possibly chronic NSAID use.

Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort.

OBJECTIVES: Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients. METHODS: We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time. RESULTS: The median baseline CES-D score (possible range 0-60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed. CONCLUSION: This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.

Aortic-vertebral interaction in ankylosing spondylitis: syndesmophyte development at the juxta-aortic vertebral rim.

OBJECTIVES: The aorta inhibits paravertebral ossification in diffuse idiopathic skeletal hyperostosis. We investigated if syndesmophytes in ankylosing spondylitis (AS) occurred less often at the vertebral rim near the aorta. METHODS: We performed thoracolumbar CT scans in 60 subjects in this cross-sectional study. The mid-thoracic spine was also scanned in 22 subjects. We divided the rim of each intervertebral disc space (IDS) into 72 angular sectors, each of 5°. We computed syndesmophyte height in each sector, and the distance from the sector to the aorta. We evaluated if syndesmophyte size or frequency in a sector was associated with its distance from the aorta. RESULTS: In the 180° region of the vertebral rim centered on the sector closest to the aorta, syndesmophyte height and/or frequency varied with the distance of the sector to the aorta, with the lowest frequency and smallest mean syndesmophyte height at the sector along the rim nearest the aorta. Additionally, syndesmophytes were less common in subjects and at IDSs where the aorta was anatomically closer to the vertebra. No syndesmophytes were present in the sector closest to the aorta in subjects whose aorta-vertebral distance was less than 2 mm, but syndesmophytes were progressively more common among subjects whose aortas lay further from the rim. CONCLUSIONS: Syndesmophytes occurred less commonly and were smaller at the thoracolumbar vertebral rim near the aorta. These findings suggest that mechanical factors extrinsic to the spine and not solely vertebral inflammation, influence syndesmophyte development in AS.

HLA class I and II alleles in susceptibility to ankylosing spondylitis.

OBJECTIVE: To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry. METHODS: HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27-negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility. RESULTS: Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA-DQB1*06:02. Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis. CONCLUSIONS: These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.

EULAR recommendations for the management of antiphospholipid syndrome in adults.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.

Interhospital variation in mortality among patients with systemic lupus erythematosus and sepsis in the USA.

OBJECTIVE: To determine whether the risk of mortality in patients with SLE hospitalized with sepsis varies among hospitals in the USA. METHODS: We used the National Inpatient Sample (2002-2011) to obtain national population-based data on outcomes for adults with SLE admitted with sepsis, and compared it with that for patients without SLE admitted with sepsis at the same hospital. We computed expected mortality based on patient demographic characteristics, comorbidities and major organ dysfunction, and calculated observed/expected (O/E) mortality ratios separately for patients with SLE and without SLE for each hospital. We then computed the ratio of these O/E ratios within hospitals to assess relative SLE mortality. We considered hospitals with a risk ratio (RR) of ⩾2.0 as having high relative SLE mortality. RESULTS: Among 424 hospitals that treated a total of 4024 patients with SLE and sepsis, the risk of in-hospital mortality varied from 0% to 60% (median 11.1%). The RR ranged from 0 to 9.75, with a median of 0.84, indicating that O/E mortality was similar in patients with and without SLE at the average hospital. Sixty-one hospitals (14.4%) had a RR of ⩾2.0, indicating higher mortality among patients with SLE. Hospitals that on average treated ⩾3.9 patients with SLE and sepsis annually were less likely to have a RR of ⩾2.0 than hospitals that treated fewer patients (10% vs 17%; P = 0.004). CONCLUSION: Mortality among patients with SLE and sepsis varied widely between hospitals, and was lower at hospitals that treated more of these patients.

Computed tomography in axial spondyloarthritis.

PURPOSE OF REVIEW: Computed tomography (CT) is increasingly being used in ankylosing spondylitis (AS) for imaging the spine and sacroiliac joint (SIJ). We review new insights to diagnosis and evaluation revealed by the use of CT. RECENT FINDINGS: Studies using low-dose CT in AS to detect syndesmophytes can image the entire spine, but semiquantitative scoring of the scans by human readers decreases the reliability and validity of this method. The thoracic spine is the segment most involved with syndesmophytes. Syndesmophytes are not randomly distributed around the vertebral rim but have preferred locations, which vary with the vertebral level and may be related to biomechanics. Examination of SIJ on abdominal CT scans has found structural changes of sacroiliitis in up to 35% of patients with inflammatory bowel disease. The significance of monosodium urate crystal deposition in the pelvis of axial spondyloarthritis patients without coexisting gout is uncertain. SUMMARY: Low-dose CT is a promising tool in AS. Studies of biomarkers or medications and their relations with syndesmophyte progression should take the thoracic spine into account. Abdominal CT scans are useful for detecting changes related to sacroiliitis.

Epidemiology of axial spondyloarthritis: an update.

PURPOSE OF REVIEW: To provide an update of the prevalence and incidence of axial spondyloarthritis in the general population and in patients with spondyloarthritis-related conditions, environmental risk factors for ankylosing spondylitis, progression from nonradiographic axial spondyloarthritis to ankylosing spondylitis, mortality, and risks for cardiovascular events in patients with ankylosing spondylitis. RECENT FINDINGS: Increasingly, administrative healthcare data have been used to study disease frequency and outcomes. The prevalence of ankylosing spondylitis ranged from 9 to 30 per 10 000 persons, which are lower than previous estimates. Data on whether childhood infections influence the risk of ankylosing spondylitis were equivocal, while having been breast-fed may be protective. Progression of patients with nonradiographic axial spondyloarthritis to ankylosing spondylitis is slow, with estimates of 5.1% in 5 years and 19% in 10 years. Risk of mortality is slightly increased in ankylosing spondylitis. Risks for cardiovascular events in ankylosing spondylitis were either not different from, or only slightly higher than in controls. No studies have examined these outcomes in the broader group of patients with axial spondyloarthritis. SUMMARY: Expanded use of administrative and registry data has facilitated studies of the epidemiology of ankylosing spondylitis, but lack of specific diagnostic codes limits use of these resources for studying axial spondyloarthritis in general.

Better Quantification of Syndesmophyte Growth in Axial Spondyloarthritis.

PURPOSE OF REVIEW: We review new insights to syndesmophyte growth in axial spondyloarthritis revealed by computed tomography (CT). RECENT FINDINGS: CT allows full reliable quantitation of syndesmophytes. About 70% of patients had detectable growth in syndesmophyte volume or height in 1 year. Syndesmophyte growth is not uniform, but can be highly heterogeneous even within the same disc space of the same patient. Syndesmophytes are not randomly distributed around the vertebral rim but have preferred locations (posterolateral and anterolateral) which vary along the spine. The frequency of syndesmophyte involvement also varies along the spine. It is highest at the thoracolumbar junction and higher in the thoracic than lumbar spine. CT syndesmophyte quantitation is a promising tool for studies of medications or biomarkers and their relations with syndesmophyte progression. The localization and growth patterns of syndesmophytes suggest importance for local factors such as mechanical stress.

Testing the construct validity of a health transition question using vignette-guided patient ratings of health.

BACKGROUND: A single-item transition question is often used to assess improvement or worsening in health, but its validity has not been tested extensively. The purpose of this study was to test the construct validity of a transition question by relating it to qualitative changes in patient's self-rating of health guided by clinical vignettes. METHODS: We studied 169 patients with active rheumatoid arthritis (RA) before and after treatment escalation. At both assessments, patients scored their current health on a rating scale after first rating three vignettes describing mild, moderate, or severe RA. We classified patients into one of these three RA categories using a nearest-neighbor match. We then related the change in these self-rated categories between visits to responses to a transition question on visit 2. RESULTS: Sixty patients improved their RA vignette category after treatment, 86 remained in the same vignette category, and 23 worsened categories. On the transition question, 101 patients reported improvement, 48 reported no change, and 20 reported worsening, representing a modest association with changes in RA vignette categories (polychoric correlation r = 0.19). The association was stronger if patients who were in the mild RA category at both visits were also classified as improved if their self-rating changed from below to above their mild vignette rating (r = 0.23) and when incorporating the importance of changes on the transition question (r = 0.26). CONCLUSION: Changes in health states, guided by clinical vignettes, support the construct validity of the transition question.