Barbara Conner-Spady

Variation in the Estimation of Quality-adjusted Life-years by Different Preference-based Instruments

Objectives. To assess the interchangeability of preference‐based health‐related quality of life tools and compare the potential gains in quality‐adjusted life years (QALYs) in patients with musculoskeletal disease. Methods. Consecutive patients visiting a rheumatology clinic completed health‐related quality of life assessments at baseline and 3, 6, and 12 months with the EuroQol (EQ‐5D), Health Utilities Index (HUI3), and Short‐Form 6D (SF‐6D). Patients rated their health changes retrospectively and responses were categorized into three groups: better, same, and worse. Correlations and repeated measures analysis of variance with post hoc contrasts and a Bonferroni correction were used to assess interchangeability of tools. Results. Results were based on 161 cases with complete baseline data and 98 cases with data at baseline and 12 months. Correlations ranged from 0.66 to 0.79. An interaction effect showed that for the better group, the EQ‐5D showed a significantly greater mean improvement (0.15) than the HUI3 (0.07) or the SF‐6D (0.05). For the worse group, the EQ‐5D showed a significantly greater mean decrease (0.19) than either the HUI3 (0.05) or the SF‐6D (0.03). QALYs differences between the better and worse groups were significantly greater (0.23) with the EQ‐5D than with the HUI3 (0.11) or the SF‐6D (0.09). Conclusions. Although results moderately support the idea that the three tools are measuring a similar underlying construct, the tools are not interchangeable because they are scaled differently and produce varying results. These findings have potential implications for the interpretation and comparability of health outcome studies and economic analyses. Possible approaches are sensitivity analysis or standardization of scores before calculation of QALYs.

Suppression of inflammation and effects on new bone formation in ankylosing spondylitis: evidence for a window of opportunity in disease modification

Objectives Although MRI data supports a link between spinal inflammation and formation of new bone in ankylosing spondylitis, anti-tumour necrosis factor α therapies have not been shown to prevent new bone formation. The authors aimed to demonstrate that while acute lesions resolve completely, more advanced lesions, characterised by evidence of reparation, are associated with new bone formation. Methods MRI scans were performed at baseline, 12 and 52 weeks in 76 ankylosing spondylitis patients recruited to a placebo-controlled trial of adalimumab therapy. New syndesmophytes were assessed on lateral radiographs of the cervical and lumbar spine at baseline and 104 weeks. Anonymised MRI scans were read independently by two readers who recorded the presence/absence of acute (type A) and advanced (type B) vertebral corner inflammatory lesions (CIL) and fat lesions. The authors used generalised linear latent and mixed models analysis to adjust for the extent of syndesmophytes/ankylosis at baseline. Results New syndesmophytes developed significantly more frequently from type B CIL (16.7%) compared with type A CIL (2.9%) (p=0.002) or no CIL (2.5%) (p<0.0001). This was also observed for both baseline and new vertebral corner fat lesions evolving over 52 weeks (11.1% (p<0.001) and 6.8% (p=0.03), respectively). The association with type B CIL (OR (95% CI 3.88, 1.20 to –12.57) and fat (OR 95% CI 4.83, 2.38– to 9.80), p<0.0001) was significant after adjustment for the extent of syndesmophytes/ankylosis at baseline. Conclusions Our data supports the hypothesis that new bone formation is more likely in advanced inflammatory lesions and proceeds through a process of fat metaplasia, supporting a window of opportunity for disease modification.

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

OBJECTIVE Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte. METHODS MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n = 38) and an observational cohort (n = 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n = 36) or anti-TNF therapy (n = 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings. RESULTS New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either feature on baseline MRI (3.1% [P = 0.008] and 1.4% [P = 0.0002], respectively). Adjusting for within-patient variations in baseline syndesmophytes/ankylosis, vertebral corners that were fat-positive/inflammation-positive significantly predicted new syndesmophytes, with an odds ratio (OR) of 7.6 (95% confidence interval [95% CI] 1.5-38.5 [P = 0.01]), while a model that included baseline variations in both fat and inflammation showed an OR of 5.8 (95% CI 2.2-15.3 [P < 0.001]) for inflammation and an OR of 1.9 (95% CI 0.9-4.1 [P = 0.1]) for fat. CONCLUSION Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.

Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index

Background: Enthesitis is a recommended core domain for assessment of ankylosing spondylitis (AS), but no measurement has yet been validated according to Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) criteria. Objective: The purpose of this study was to seek to validate an enthesitis index for patients with AS according to OMERACT criteria. Methods: An enthesitis index was validated in two AS patient cohorts: (1) a longitudinal cohort (n = 223) and (2) 22 patients from three Canadian sites participating in a 24-week randomised placebo-controlled trial of adalimumab in AS. Construct validity was evaluated by correlation analysis with the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI) and quality of life instruments. Reproducibility was assessed by intraclass correlation coefficient (ICC), and responsiveness was assessed by Guyatt’s effect size and standardised response mean. Results: The most frequently affected sites were the greater trochanter and supraspinatus insertion (∼20%). Patients with enthesitis had significantly greater scores for the BASDAI, BASFI, patient global, AS-specific quality of life index (ASQOL) and the Short Form 36 (SF-36) General Health Survey (p<0.001). The enthesitis score contributed significantly to variance in the BASDAI and BASFI. Interobserver ICCs were 0.96 in the longitudinal cohort and 0.89 and 0.77 in the adalimumab clinical trial cohort (for status and change score, respectively). Significant differences in change scores were evident for all patients after 24 weeks of adalimumab treatment, (p = 0.04), this being more significant when a subset of the most commonly affected entheses were analysed (p = 0.01). Conclusion: AS patients with enthesitis constitute a more severe subset of disease, and the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index is feasible and reliable for measurement of this condition. Discrimination requires further study in larger trials.

Systematic Assessment of Inflammation by Magnetic Resonance Imaging in the Posterior Elements of the Spine in Ankylosing Spondylitis

Magnetic resonance imaging (MRI) is sensitive for scoring inflammatory lesions in the spine, but attention has primarily focused on vertebral bodies, and no study has systematically examined the posterior elements. We aimed to systematically determine the frequency and distribution of inflammatory changes in the posterior elements of the spine using MRI, and to assess the reliability of their detection and their impact on discrimination of spinal MRI.

Appropriateness of healthcare interventions: Concepts and scoping of the published literature

OBJECTIVES This report is a scoping review of the literature with the objective of identifying definitions, conceptual models and frameworks, as well as the methods and range of perspectives, for determining appropriateness in the context of healthcare delivery. METHODS To lay groundwork for future, intervention-specific research on appropriateness, this work was carried out as a scoping review of published literature since 1966. Two reviewers, with two screens using inclusion/exclusion criteria based on the objective, focused the research and articles chosen for review. RESULTS The first screen examined 2,829 abstracts/titles, with the second screen examining 124 full articles, leaving 37 articles deemed highly relevant for data extraction and interpretation. Appropriateness is defined largely in terms of net clinical benefit to the average patient and varies by service and setting. The most widely used method to assess appropriateness of healthcare services is the RAND/UCLA Model. There are many related concepts such as medical necessity and small-areas variation. CONCLUSIONS A broader approach to determining appropriateness for healthcare interventions is possible and would involve clinical, patient and societal perspectives.

Magnetic resonance imaging assessment of spinal inflammation in ankylosing spondylitis: standard clinical protocols may omit inflammatory lesions in thoracic vertebrae.

OBJECTIVE Radiologic assessment of spinal inflammation in patients with ankylosing spondylitis (AS) relies primarily on magnetic resonance imaging (MRI), although little is known about the distribution of inflammatory lesions within the structures of the spine. Our objective was to compare the distribution of inflammatory lesions centrally and laterally within the thoracic and lumbar spine vertebral bodies. METHODS We studied 49 patients with AS who were scanned with STIR and T1-weighted spin-echo MRI of the whole spine. Scans were read by 2 musculoskeletal radiologists, with a third reader as the arbitrator. Controls included 6 age-matched individuals. We recorded bone marrow edema on STIR images from each vertebral body, separately identifying central and lateral slices. The latter were defined as images that included or were lateral to the pedicle. Interreader reproducibility was assessed by kappa statistics. RESULTS Inflammation was present in 263 (45%) of 588 thoracic and 86 (35%) of 245 lumbar vertebrae; the mean number of affected thoracic and lumbar vertebrae per patient were 5.4 and 1.8, respectively. Inflammation was present in the lateral aspect of 219 (37%) of 588 thoracic vertebrae and 45 (18%) of 245 lumbar vertebrae (P < 0.001). Lesions were more common laterally than centrally for all thoracic vertebrae except for T7. Involvement of only the lateral slices was observed in as many as 19.6% of thoracic vertebrae. CONCLUSION Evaluation of spinal inflammation by MRI may omit lesions in up to 20% of inflamed thoracic vertebrae if both scanning and image assessment do not include sagittal slices that extend to the lateral edges of all vertebrae.

Prioritization of patients on waiting lists for hip and knee replacement: Validation of a priority criteria tool

OBJECTIVES This study tested the reliability and validity of the Western Canada Waiting List Project priority criteria score (PCS) for prioritizing patients waiting for hip and knee arthroplasty. METHODS Sixteen orthopedic surgeons assessed 233 consecutive patients at consultation for hip or knee arthroplasty. Measures included the PCS, a visual analogue scale of urgency (VAS urgency), and maximum acceptable waiting time (MAWT). Patients completed a VAS urgency, an MAWT, the Western Ontario McMaster Osteoarthritis Index (WOMAC), and the EQ-5D. Using correlational analysis, convergent and discriminant validity was assessed between similar constructs in the priority criteria and WOMAC. Median MAWTs were determined for five levels of urgency based on PCS percentiles. Internal consistency reliability was assessed with Cronbachs alpha. RESULTS The sample of 233 patients (62 percent female) ranged in age from 18 to 89 years (mean, 66.3 years). A total of 45 percent were booked for hip and 55 percent for knee arthroplasty. Correlations were strong between the PCS and surgeon VAS urgency (r = .79) and weaker between patient and surgeon measures of VAS urgency (r = .24) and MAWT (r = .44). Correlation coefficients between similar constructs in the priority criteria and WOMAC ranged from 0.24 to 0.32 and were higher than those measuring dissimilar constructs. For decreasing levels of urgency, the median MAWT ranged from 10 to 12 weeks for surgeons and 4 to 12 weeks for patients. Cronbachs alpha was 0.79. CONCLUSIONS Results support the validity of the PCS as a measure of surgeon-rated urgency. Patients might be ranked differently with different prioritization measures.

Relative urgency for referral from primary care to rheumatologists: The Priority Referral Score

Timely access to rheumatology consultation is fundamental to appropriate and effective management of patients with musculoskeletal and autoimmune diseases. Yet, for a variety of reasons, limited and delayed access is commonplace. Moreover, information exchange for referral is often inadequate or poorly communicated. The objective of this work was to improve referral from primary care to rheumatology by formulating and testing a clinically coherent, reliable, and non–diagnosis‐dependent Priority Referral Score (PRS).

Responsiveness of the EuroQol in breast cancer patients undergoing high dose chemotherapy

Objective: To assess the responsiveness of the EuroQol (EQ-5D) by comparing it with the Functional Living Index-Cancer (FLIC) and a self-reported rating of health-related quality of life (HRQL). Methods: HRQL was measured four times during the course of high dose chemotherapy (HDC) and bone marrow transplantation in 40 patients with stage II and III breast cancer. Measurements were at baseline (T1), pre-HDC (T2), 3 weeks post-HDC (T3), and 3 months post-HDC (T4). Results: Effect size ranged from 1.16 (T1–T3) to 0.66 (T3–T4) for the EQ-5D and 0.85–0.91 respectively for the FLIC. No significant differences in effect sizes between the EQ-5D and the FLIC were found. Repeated measures ANOVA yielded a significant change for all measures, with HRQL decreasing post-HDC and returning to baseline levels by 3 m post-HDC. EQ-5D dimensions changed significantly over time for mobility, self-care, and usual activities. EQ-5D index scores at T3 had a bimodal distribution. Interpretation of psychological changes was facilitated by an analysis of FLIC items. Conclusions: The EQ-5D is responsive to the clinically large changes associated with HDC in breast cancer patients. The bimodal distribution of the EQ-5D index has implications for the interpretation of EQ-5D change scores.