Embedding stakeholder preferences in setting priorities for health research: Using a discrete choice experiment to develop a multi-criteria tool for evaluating research proposals.

We determined weights for a multi-criteria tool for assessing the relative merits of clinical-trial research proposals, and investigated whether the weights vary across relevant stakeholder groups. A cross-sectional, adaptive discrete choice experiment using 1000minds online software was administered to consumers, researchers and funders affiliated with the Australian Clinical Trials Alliance (ACTA). We identified weights for four criteria-Appropriateness, Significance, Relevance, Feasibility-and their levels, representing their relative importance, so that research proposals can be scored between 0% (nil or very low merit) and 100% (very high merit). From 220 complete survey responses, the most important criterion was Appropriateness (adjusted for differences between stakeholder groups, mean weight 28.9%) and the least important was Feasibility (adjusted mean weight 19.5%). Consumers tended to weight Relevance more highly (2.7% points difference) and Feasibility less highly (3.1% points difference) than researchers. The research or grant writing experience of researchers or consumers was not associated with the weights. A multi-criteria tool for evaluating research proposals that reflects stakeholders' preferences was created. The tool can be used to assess the relative merits of clinical trial research proposals and rank them, to help identify the best proposals for funding.

Gout Remission as a Goal of Urate-Lowering Therapy: A Critical Review.

Urate-lowering therapies for the management of gout lead to a reduction in serum urate levels, monosodium urate crystal deposition, and the clinical features of gout, including painful and disabling gout flares, chronic gouty arthritis, and tophi. Thus, disease remission is a potential goal of urate-lowering therapy. In 2016, preliminary gout remission criteria were developed by a large group of rheumatologists and researchers with expertise in gout. The preliminary gout remission criteria were defined as: serum urate < 0.36 mmol/L (6 mg/dL); an absence of gout flares; an absence of tophi; pain due to gout < 2 on a 0-10 scale; and a patient global assessment < 2 on a 0-10 scale over a 12-month period. In this critical review, we describe the development of the preliminary gout remission criteria, the properties of the preliminary gout remission criteria, and clinical studies of gout remission in people taking urate-lowering therapy. We also describe a future research agenda for gout remission.

Urate-lowering therapy following a treat-to-target continuation strategy compared to a treat-to-avoid-symptoms discontinuation strategy in gout patients in remission (GO TEST Finale): study protocol of a multicentre pragmatic randomized superiority trial.

BACKGROUND: Long-term gout treatment is based on reducing serum urate levels using urate-lowering therapy (ULT). Most guidelines recommend using a lifelong continuation treat-to-target (T2T) strategy, in which ULT is dosed or combined until a serum urate target has been reached and maintained. However, a frequently used alternative strategy in clinical practice is a treat-to-avoid-symptoms (T2S) ULT discontinuation strategy, with the possibility of restarting the medication. This latter strategy aims at an acceptable symptom state, regardless of serum urate levels. High-quality evidence to support either strategy for patients in prolonged remission while using ULT is lacking. METHODS: We developed an investigator-driven pragmatic, open-label, multicentre, randomized, superiority treatment strategy trial (GO TEST Finale). At least 278 gout patients using ULT who are in remission (>12 months, preliminary gout remission criteria) will be randomized 1:1 to a continued T2T strategy (treatment target serum urate < 0.36 mmol/l) or switched to a T2S discontinuation strategy in which ULT is tapered to stop and restarted in case of (persistent or recurrent) flaring. The primary outcome is the between-group difference in the proportion of patients not in remission during the last 6 months of 24 months follow-up and will be analyzed using a two proportion z test. Secondary outcomes are group differences in gout flare incidence, reintroduction or adaptation of ULT, use of anti-inflammatory drugs, serum urate changes, occurrence of adverse events (with a special interest in cardiovascular and renal events), and cost-effectiveness. DISCUSSION: This study will be the first clinical trial comparing two ULT treatment strategies in patients with gout in remission. It will contribute to more specific and unambiguous guideline recommendations and improved cost-effectiveness of long-term gout treatment. It also paves the way (exploratory) to individualized long-term ULT treatment. In this article, we elaborate on some of our trial design choices and their clinical and methodological consequences. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP) NL9245. Registered on 2 February 2021 (METC Oost-Nederland NL74350.091.20); EudraCT EUCTR2020-005730-15-NL. Registered on 11 January 2021.

Outcome reporting in randomized trials in gout: A systematic scoping review from the OMERACT gout working group assessing the uptake of the core outcome set.

OBJECTIVE: The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement. METHODS: We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www. CLINICALTRIALS: gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study 'Acute trials' reflect studies that describe interventions for short term management of gout flares, and 'chronic trials' describe interventions for long-term urate lowering therapy in the management of gout. RESULTS: From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time. CONCLUSION: In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting. REGISTRATION: Prospero: CRD42019151316.

Which clinical research questions are the most important? Development and preliminary validation of the Australia & New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network Research Question Importance Tool (ANZMUSC-RQIT).

BACKGROUND AND AIMS: High quality clinical research that addresses important questions requires significant resources. In resource-constrained environments, projects will therefore need to be prioritized. The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network aimed to develop a stakeholder-based, transparent, easily implementable tool that provides a score for the 'importance' of a research question which could be used to rank research projects in order of importance. METHODS: Using a mixed-methods, multi-stage approach that included a Delphi survey, consensus workshop, inter-rater reliability testing, validity testing and calibration using a discrete-choice methodology, the Research Question Importance Tool (ANZMUSC-RQIT) was developed. The tool incorporated broad stakeholder opinion, including consumers, at each stage and is designed for scoring by committee consensus. RESULTS: The ANZMUSC-RQIT tool consists of 5 dimensions (compared to 6 dimensions for an earlier version of RQIT): (1) extent of stakeholder consensus, (2) social burden of health condition, (3) patient burden of health condition, (4) anticipated effectiveness of proposed intervention, and (5) extent to which health equity is addressed by the research. Each dimension is assessed by defining ordered levels of a relevant attribute and by assigning a score to each level. The scores for the dimensions are then summed to obtain an overall ANZMUSC-RQIT score, which represents the importance of the research question. The result is a score on an interval scale with an arbitrary unit, ranging from 0 (minimal importance) to 1000. The ANZMUSC-RQIT dimensions can be reliably ordered by committee consensus (ICC 0.73-0.93) and the overall score is positively associated with citation count (standardised regression coefficient 0.33, p<0.001) and journal impact factor group (OR 6.78, 95% CI 3.17 to 14.50 for 3rd tertile compared to 1st tertile of ANZMUSC-RQIT scores) for 200 published musculoskeletal clinical trials. CONCLUSION: We propose that the ANZMUSC-RQIT is a useful tool for prioritising the importance of a research question.

Approaches to prioritising research for clinical trial networks: a scoping review.

BACKGROUND: Prioritisation of clinical trials ensures that the research conducted meets the needs of stakeholders, makes the best use of resources and avoids duplication. The aim of this review was to identify and critically appraise approaches to research prioritisation applicable to clinical trials, to inform best practice guidelines for clinical trial networks and funders. METHODS: A scoping review of English-language published literature and research organisation websites (January 2000 to January 2020) was undertaken to identify primary studies, approaches and criteria for research prioritisation. Data were extracted and tabulated, and a narrative synthesis was employed. RESULTS: Seventy-eight primary studies and 18 websites were included. The majority of research prioritisation occurred in oncology and neurology disciplines. The main reasons for prioritisation were to address a knowledge gap (51 of 78 studies [65%]) and to define patient-important topics (28 studies, [35%]). In addition, research organisations prioritised in order to support their institution's mission, invest strategically, and identify best return on investment. Fifty-seven of 78 (73%) studies used interpretative prioritisation approaches (including Delphi surveys, James Lind Alliance and consensus workshops); six studies used quantitative approaches (8%) such as prospective payback or value of information (VOI) analyses; and 14 studies used blended approaches (18%) such as nominal group technique and Child Health Nutritional Research Initiative. Main criteria for prioritisation included relevance, appropriateness, significance, feasibility and cost-effectiveness. CONCLUSION: Current research prioritisation approaches for groups conducting and funding clinical trials are largely interpretative. There is an opportunity to improve the transparency of prioritisation through the inclusion of quantitative approaches.

Is repeat serum urate testing superior to a single test to predict incident gout over time?

Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3-5 years apart, followed by an assessment of gout incidence 5-6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9-10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 µmol/L (5.42 mg/dL) vs. 340 µmol/L (5.71 mg/dL), P<0.001) which were a mean of 3.5 years apart, but the first and second measures were highly correlated (r = 0.81, P<0.001). No differences were observed in the predictive ability of incident gout between the four measures of serum urate measurement with ROC curve AUC statistics ranging between 0.81 (95% confidence intervals: 0.78-0.84) and 0.84 (95% confidence intervals: 0.81-0.87). These data show that repeat serum urate testing is not superior to a single measure of serum urate for prediction of incident gout over approximately one decade.

Gout Flare Severity From the Patient Perspective: A Qualitative Interview Study.

OBJECTIVE: The patient experience of a gout flare is multidimensional. To establish the most appropriate methods of flare measurement, there is a need to understand the complete experience of a flare. This qualitative study aimed to examine what factors contribute to the severity of a flare from the patient perspective. METHODS: Face-to-face interviews were conducted with patients with gout. Participants were asked to share their experience with their worst gout flare and contrast it to their experience of a less severe or mild flare. Interviews were audio recorded and transcribed verbatim. Data were analyzed using a reflexive thematic approach. RESULTS: In total, 22 participants with gout (17 male participants, mean age 66.5 years) were interviewed at an academic center in Auckland, New Zealand. Four key themes were identified as contributing to the severity of a flare: 1) flare characteristics (pain intensity, joint swelling, redness and warmth, duration, and location); 2) impact on function (including walking, activities of daily living, wearing footwear, and sleep); 3) impact on family and social life (dependency on others, social connection, and work); and 4) psychological impact (depression, anxiety, irritability, and sense of control). CONCLUSION: A wide range of interconnecting factors contribute to the severity of a gout flare from the patient perspective. Capturing these domains in long-term gout studies would provide a more meaningful and accurate representation of cumulative flare burden.

Identifying Potential Classification Criteria for Calcium Pyrophosphate Deposition Disease: Item Generation and Item Reduction.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Which Attributes Are Most and Least Important to Patients When Considering Gout Flare Burden Over Time? A Best-worst Scaling Choice Study.

OBJECTIVE: Several factors contribute to the patient experience of gout flares, including pain intensity, duration, frequency, and disability. It is unknown which of these factors are most important to patients when considering flare burden over time, including those related to the cumulative experience of all flares, or the experience of a single worst flare. This study aimed to determine which flare attributes are the most and least important to the patient experience of flare burden over time. METHODS: Participants with gout completed an anonymous online survey. Questions were aimed at identifying which attributes of gout flares, representing both individual and cumulative flare burden, were the most and least important over a hypothetical 6-month period. A best-worst scaling method was used to determine the importance hierarchy of the included attributes. RESULTS: Fifty participants were included. Difficulty doing usual activities during the worst flare and pain of the worst flare were ranked as the most important, whereas average pain of all flares was considered the least important. Overall, attributes related to the single worst gout flare were considered more important than attributes related to the cumulative impact of all flares. CONCLUSION: When thinking about the burden of gout flares over time, patients rank activity limitation and pain experienced during their worst gout flare as the most important contributing factors, whereas factors related to the cumulative impact of all flares over time are relatively less important.

Economic analysis of the 'Take Charge' intervention for people following stroke: Results from a randomised trial.

OBJECTIVE: To undertake an economic analysis of the Take Charge intervention as part of the Taking Charge after Stroke (TaCAS) study. DESIGN: An open, parallel-group, randomised trial comparing active and control interventions with blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: The Take Charge intervention, a strengths based, self-directed rehabilitation intervention, in two doses (one or two sessions), and a control intervention (no Take Charge sessions). MEASURES: The cost per quality-adjusted life year (QALY) saved for the period between randomisation (always post hospital discharge) and 12 months following acute stroke. QALYs were calculated from the EuroQol-5D-5L. Costs of stroke-related and non-health care were obtained by questionnaire, hospital records and the New Zealand Ministry of Health. RESULTS: One-year post hospital discharge cost of care was mean (95% CI) $US4706 (3758-6014) for the Take Charge intervention group and $6118 (4350-8005) for control, mean (95% CI) difference $ -1412 (-3553 to +729). Health utility scores were mean (95% CI) 0.75 (0.73-0.77) for Take Charge and 0.71 (0.67-0.75) for control, mean (95% CI) difference 0.04 (0.0-0.08). Cost per QALY gained for the Take Charge intervention was $US -35,296 (=£ -25,524, € -30,019). Sensitivity analyses confirm Take Charge is cost-effective, even at a very low willingness-to-pay threshold. With a threshold of $US5000 per QALY, the probability that Take Charge is cost-effective is 99%. CONCLUSION: Take Charge is cost-effective and probably cost saving.

The GOUT-36 prediction rule for inpatient gout flare in people with comorbid gout: derivation and external validation.

OBJECTIVES: To develop and validate a gout flare risk stratification tool for people with gout hospitalized for non-gout conditions. METHODS: The prediction rule for inpatient gout flare was derived from a cohort of 625 hospitalized people with comorbid gout from New Zealand. The rule had four items: no pre-admission gout flare prophylaxis, no pre-admission urate-lowering therapy, tophus and pre-admission serum urate >0.36 mmol/l within the previous year (GOUT-36 rule). Two or more items are required for the classification of high risk for developing inpatient gout flares. The GOUT-36 rule was validated in a prospective cohort of 284 hospitalized people with comorbid gout from Thailand and China. RESULTS: The GOUT-36 rule had a sensitivity of 75%, specificity of 67% and area under the curve of 0.71 for classifying people at high risk for developing inpatient gout flares. Four risk groups were developed: low (no items), moderate (one item), high (two items) and very high risk (three or four items). In a population with frequent (overall 34%) in-hospital gout flares, 80% of people with very high risk developed inpatient flares while 11% with low risk had inpatient flares. CONCLUSION: The GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flares. The rule may help inform clinical decisions and future research on the prevention of inpatient gout flares.

Regular pre-admission urate-lowering therapy and serum urate testing are associated with a shorter hospital length of stay in people with gout: A nation-wide population-based cohort study.

OBJECTIVE: This study aims to explore the association between inpatient gout flare-related variables and the length of stay (LOS) in hospitalized people with comorbid gout. METHODS: Using data from the Aotearoa/New Zealand national data collections, this cohort study included adults with comorbid gout who were admitted to publicly funded hospitals during 2017 for reasons other than gout. The primary outcome was LOS. Association between 20 variables and the LOS was explored using two generalized linear models. Directed acyclic graph (DAG) was constructed to evaluate the causal relationship between pre-admission urate lowering therapy (ULT) and LOS. RESULTS: The cohort included 36 047 admissions. We identified five variables associated with shorter LOS (pre-admission regular urate-lowering therapy (ULT), serum urate testing, male gender, Maori ethnicity and low-dose aspirin) and seven variables associated with longer LOS (M3 multimorbidity index, acute admission, operation, loop diuretics, potassium-sparing diuretics, NSAIDs, and age). Regular ULT had the strongest impact on shorter LOS (10% shorter). The model estimated an additional four days of hospitalization if the patient had multiple variables associated with longer LOS. DAG suggested a causal relationship between regular ULT and LOS under the condition that all unobserved confounders affected only ULT use, with no impact on in-hospital gout flares and/or LOS except through its influence on ULT use or as mediator of confounders that were observed. CONCLUSION: We have identified a set of gout flare-related variables found to be associated with LOS in hospitalized people with comorbid gout. Pre-admission ULT may help reduce the LOS in such patients.

Association between serum urate and flares in people with gout and evidence for surrogate status: a secondary analysis of two randomised controlled trials.

BACKGROUND: Use of serum urate as a treatment target and outcome measure has become controversial in view of the 2017 American College of Physicians guidelines, which advocated a treat-to-symptom rather than a treat-to-target serum urate approach to gout management. The relevance of serum urate as a treatment target measure implies that achievement of target serum urate is causally associated with improvement in patient-important outcomes such as reduction in the number of gout flares. The aim of this study was to assess the causal relationship between achieving target serum urate and the occurrence of gout flares. METHODS: We analysed individual patient-level data from two randomised trials on urate-lowering therapies in people with gout conducted in Nottingham, UK, and New Zealand. We included participants randomly assigned to immediate dose escalation in the New Zealand study and all participants in the Nottingham study (a nurse-led gout care group and a general practitioner-led usual care group). Individuals who on average achieved a serum urate concentration less than 6 mg/dL (0·36 mmol/L) based on data at 6, 9, and 12 months post-baseline were defined as serum urate responders. The primary outcome was the proportion of participants having at least one gout flare, and the secondary outcome was the mean number of flares per participant per month, from 12 to 24 months after baseline, compared between serum urate responders and non-responders. In adjusted logistic regression models, serum urate at baseline, previous flare history (in the year preceding study entry), presence of tophi at baseline, and, for the Nottingham dataset, the original randomisation group, were included as covariates. The Nottingham study was registered with ClinicalTrials.gov, NCT01477346. The New Zealand study was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000845932. FINDINGS: From the combined individual data from both trials, we identified 343 serum urate responders and 245 serum urate non-responders. Significantly fewer serum urate responders had a gout flare than did serum urate non-responders between 12 and 24 months (91 [27%] of 343 vs 156 [64%] of 245; adjusted odds ratio [OR] 0·29 [95% CI 0·17 to 0·51], p<0·0001). The mean number of flares per participant per month between 12 and 24 months was significantly lower in serum urate responders than in serum urate non-responders (adjusted mean difference -1·41 [95% CI -1·77 to -1·04], p<0·0001). This association was independent of the original randomised treatment allocation. INTERPRETATION: Achieving an average serum urate concentration less than 6 mg/dL is associated with an absence of gout flares and a reduction in the number of flares in the subsequent 12 months in people with gout. These results support a treat-to-target serum urate approach in the management of gout. FUNDING: None.

Serum urate as a proposed surrogate outcome measure in gout trials: From the OMERACT working group.

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).

What Represents Treatment Efficacy in Long-term Studies of Gout Flare Prevention? An Interview Study of People With Gout.

OBJECTIVE: The patient experience of gout flares is multidimensional, with several contributing factors including pain intensity, duration, and frequency. There is currently no consistent method for reporting gout flare burden in long-term studies. This study aimed to determine which factors contribute to patient perceptions of treatment efficacy in long-term studies of gout flare prevention. METHODS: This study involved face-to-face interviews with people with gout using visual representations of gout flare patterns. Participants were shown different flare scenarios over a hypothetical 6-month treatment period that portrayed varying flare frequency, pain intensity, and flare duration. The participants were asked to indicate and discuss which scenario they believed was most indicative of successful treatment over time. Quantitative data relating to the proportion of participants selecting each scenario were reported using descriptive statistics. A qualitative descriptive approach was used to code and categorize the data from the interview transcripts. RESULTS: Twenty-two people with gout participated in the semistructured interviews. All 3 factors of pain intensity, flare duration, and flare frequency influenced participants' perception of treatment efficacy. However, a shorter flare duration was the most common indicator of successful treatment, with half of participants (n = 11, 50%) selecting the scenario with a shorter flare duration over those with less painful flares. CONCLUSION: Flare duration, flare frequency, and pain severity are all taken into account by patients with gout when considering treatment efficacy over time. Long-term studies of gout should ideally capture all these factors to better represent patients' experience of treatment success.

Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group.

INTRODUCTION: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets. METHODS: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets. FINDINGS: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD. CONCLUSION: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA).

Care of patients with early inflammatory arthritis in the Wellington region according to the British Society of Rheumatology's best practice tariff standards.

AIM: To compare the care of patients with suspected early inflammatory arthritis (EIA) in the Wellington region with the quality standards from the British Society of Rheumatology (BSR) 2013/14 best practice tariffs. METHODS: The case notes for patients first seen in clinic from the beginning of 2015 were reviewed until at least 100 cases of suspected inflammatory arthritis were identified. Data gathered included the length of time from referral to first specialist rheumatology clinic, the length of time from referral to the commencement of disease modifying therapy for cases of inflammatory arthritis and the number of specialist-led clinics within the first 12 months of the first appointment. RESULTS: 117 cases of suspected inflammatory arthritis were reviewed. The median time from referral to the first appointment was 11.4 weeks (IQR 6.6-13.3). 61 of the 117 cases had clinically confirmed EIA. The median time from referral to the commencement of disease-modifying therapy was 10.5 weeks (IQR 5-15). For confirmed EIA, the median number of clinics in the first year was four (IQR 3-4). CONCLUSION: Patients with suspected inflammatory arthritis in the Wellington region wait much longer to be seen than is recommended by the BSR guidelines.

The effect of the Take Charge intervention on mood, motivation, activation and risk factor management: Analysis of secondary data from the Taking Charge after Stroke (TaCAS) trial.

OBJECTIVE: To use secondary data from the Taking Charge after Stroke study to explore mechanisms for the positive effect of the Take Charge intervention on physical health, advanced activities of daily living and independence for people after acute stroke. DESIGN: An open, parallel-group, randomised trial with two active and one control intervention and blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: One, two, or zero sessions of the Take Charge intervention, a self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. MEASURES: Twelve months after stroke: Mood (Patient Health Questionnaire-2, Mental Component Summary of the Short Form 36); 'ability to Take Charge' using a novel measure, the Autonomy-Mastery-Purpose-Connectedness (AMP-C) score; activation (Patient Activation Measure); body mass index (BMI), blood pressure (BP) and medication adherence (Medication Adherence Questionnaire). RESULTS: Follow-up was near-complete (388/390 (99.5%)) of survivors at 12 months. Mean age (SD) was 72.0 (12.5) years. There were no significant differences in mood, activation, 'ability to Take Charge', medication adherence, BMI or BP by randomised group at 12 months. There was a significant positive association between baseline AMP-C scores and 12-month outcome for control participants (1.73 (95%CI 0.90 to 2.56)) but not for the Take Charge groups combined (0.34 (95%CI -0.17 to 0.85)). CONCLUSION: The mechanism by which Take Charge is effective remains uncertain. However, our findings support a hypothesis that baseline variability in motivation, mastery and connectedness may be modified by the Take Charge intervention.

Axial spondyloarthritis: concept, construct, classification and implications for therapy.

The axial spondyloarthritis (axSpA) disease concept has undergone substantial change from when the entity ankylosing spondylitis was defined by the modified New York criteria in 1984. Developments in imaging, therapy and genetics have all contributed to changing the concept of axSpA from one of erosions in the sacroiliac joints to a spectrum of disease with and without changes evident on plain radiographs. Changes to the previously held concept and construct of the disease have also necessitated new classification criteria. The use of MRI, primarily of the sacroiliac joints, has substantially altered the diagnosis and differential diagnosis of axSpA. Many in the axSpA community believe that the current classification criteria lack specificity, and the CLASSIC study is underway to examine this area. Although much about the evolving axSpA disease concept is universally agreed, there remains disagreement about operationalizing aspects of it, such as the requirement for the objective demonstration of axial inflammation for the classification of axSpA. New imaging technologies, biomarkers and genetics data will probably necessitate ongoing revision of axSpA classification criteria. Advances in our knowledge of the biology of axSpA will settle some differences in opinion as to how the disease concept is applied to the classification and diagnosis of patients.