Population characteristics as important contextual factors in rheumatological trials: an exploratory meta-epidemiological study from an OMERACT Working Group.

OBJECTIVES: To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions. METHODS: In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses. RESULTS: We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion. CONCLUSIONS: This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials. PROSPERO REGISTRATION NUMBER: CRD42019127642.

The Global Burden of Musculoskeletal Pain-Where to From Here?

To summarize the current understanding of the global burden of musculoskeletal pain-related conditions, consider the process of evidence generation and the steps to generate global pain estimates, identify key gaps in our understanding, and propose an agenda to address these gaps, we performed a narrative review. In the 2010 Global Burden of Disease Study (GBD), which broadened the scope of musculoskeletal conditions that were included over previous rounds, low back pain imposed the highest disability burden of all specific conditions assessed, and subsequent GBD reports further reinforce the size of this burden. Over the past decade, the GBD has produced compelling evidence of the leading contribution of musculoskeletal pain conditions to the global burden of disability, but this has not translated into global health policy initiatives. However, system- and service-level responses to the disease burden persist across high-, middle-, and low-income settings. There is a mismatch between the burden of musculoskeletal pain conditions and appropriate health policy response and planning internationally that can be addressed with an integrated research and policy agenda.

Reflecting on the global burden of musculoskeletal conditions: lessons learnt from the global burden of disease 2010 study and the next steps forward.

The objective of this paper is to provide an overview of the strengths, limitations and lessons learned from estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It should be read in conjunction with the other GBD 2010 Study papers published in this journal. The strengths of the GBD 2010 Study include: the involvement of a MSK expert group; development of new and more valid case definitions, functional health states, and disability weights to better reflect the MSK conditions; the extensive series of systematic reviews undertaken to obtain data to derive the burden estimates; and the use of a new, more advanced version of the disease-modelling software (DisMod-MR). Limitations include: many regions of the world did not have data; the extent of heterogeneity between included studies; and burden does not include broader aspects of life, such as participation and well-being. A number of lessons were learned. Ongoing involvement of experts is critical to ensure the success of future efforts to quantify and monitor this burden. A paradigm shift is urgently needed among global agencies in order to alleviate the rapidly increasing global burden from MSK conditions. Prevention and control of MSK disability are required, along with health system changes. Further research is needed to improve understanding of the predictors and clinical course across different settings, and the ways in which MSK conditions can be better managed and prevented.

Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients.

OBJECTIVE: The aim of this study was to examine the impact of smoking on health-related quality of life (HRQoL) among AS patients who were taking biologic DMARDS. METHODS: This is a longitudinal cohort study of AS patients with anti-TNF treatment in the Australian Rheumatology Association Database (2003-11). They were assessed using the 36-item Short Form Health Survey (SF-36), Assessment of Quality of Life (AQoL) and HAQ for spondylitis (HAQ-S) on a biannual basis. Linear mixed models were used to assess the impact of smoking on HRQoL outcomes over the first 2 years of treatment. RESULTS: Four hundred and twenty-two patients [73% male, mean age 44.9 years (s.d. 12.7) provided 1189 assessments for the study. Current smokers (n = 79) were slightly younger, more likely to be male, less likely to use or to have previously used prednisolone and had a slightly shorter disease duration than past smokers (n = 138) or non-smokers (n = 205). After adjusting for smoking, gender, age, education, employment, co-morbidities and medication use, including DMARDs, anti-inflammatories and analgesics, all the HRQoL measures improved significantly over the study period and the improvements were not modified by smoking status (all P-values >0.36). Current smokers tended to have a poorer HRQoL on the SF-36 physical score [-1.93 (95% CI -3.94, 0.09), P = 0.06] and the HAQ-S score [0.10 (95% CI -0.01, 0.20), P = 0.07] compared with non-smokers. CONCLUSION: Among AS patients, active smoking did not diminish or modify the improvements in HRQoL from anti-TNF treatment, even though current smokers compared with non-smokers tended to have poorer scores in some HRQoL measures.

The global burden of musculoskeletal conditions for 2010: an overview of methods.

The objective of this paper is to provide an overview of methods used for estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Diseases 2010 study. It should be read in conjunction with the disease-specific MSK papers published in Annals of Rheumatic Diseases. Burden estimates (disability-adjusted life years (DALYs)) were made for five specific MSK conditions: hip and/or knee osteoarthritis (OA), low back pain (LBP), rheumatoid arthritis (RA), gout and neck pain, and an 'other MSK conditions' category. For each condition, the main disabling sequelae were identified and disability weights (DW) were derived based on short lay descriptions. Mortality (years of life lost (YLLs)) was estimated for RA and the rest category of 'other MSK', which includes a wide range of conditions such as systemic lupus erythematosus, other autoimmune diseases and osteomyelitis. A series of systematic reviews were conducted to determine the prevalence, incidence, remission, duration and mortality risk of each condition. A Bayesian meta-regression method was used to pool available data and to predict prevalence values for regions with no or scarce data. The DWs were applied to prevalence values for 1990, 2005 and 2010 to derive years lived with disability. These were added to YLLs to quantify overall burden (DALYs) for each condition. To estimate the burden of MSK disease arising from risk factors, population attributable fractions were determined for bone mineral density as a risk factor for fractures, the occupational risk of LBP and elevated body mass index as a risk factor for LBP and OA. Burden of Disease studies provide pivotal guidance for governments when determining health priority areas and allocating resources. Rigorous methods were used to derive the increasing global burden of MSK conditions.

Models of care for musculoskeletal health in Australia: now more than ever to drive evidence into health policy and practice.

Musculoskeletal health conditions such as arthritis, osteoporosis and pain syndromes impart a profound socioeconomic burden worldwide, particularly in developed nations such as Australia. Despite the identified burden, substantial evidence-practice and care disparity gaps remain in service delivery and access that limit the potential for improved consumer outcomes and system efficiencies. Addressing these gaps requires a whole-of-sector response, supported by evidence-informed health policy. Models of care (MoCs) serve as a policy vehicle to embed evidence into health policy and guide practice through changes in service delivery systems and clinician behaviour. In Australia, MoCs for musculoskeletal health have been developed by networks of multidisciplinary stakeholders and are incrementally being implemented across health services, facilitated by dedicated policy units and clinical champions. A web of evidence is now emerging to support this approach to driving evidence into health policy and practice. Understanding the vernacular of MoCs and the development and implementation of MoCs is important to embracing this approach to health policy.

Health Perceptions, Multimorbidity, and New Fractures and Mortality Among Patients With a Fracture.

Importance: A high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored. Objective: To examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture. Design, Setting, and Participants: This prospective cohort study included participants from New South Wales, Australia, in the Sax Institute's 45 and Up Study (n = 267 357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023. Exposures: Charlson Comorbidity Index (CCI) score and self-rated health (SRH). Main Outcomes and Measures: The main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males. Results: Of 25 280 adults who sustained incident fractures, 16 191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher. Conclusions and Relevance: In this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.

Pregnancy outcomes in women with juvenile idiopathic arthritis: a population-based study.

OBJECTIVE: The aim of this study is to describe pregnancy outcomes among women with JIA. METHODS: Women who gave birth in New South Wales (NSW), Australia, were linked to hospital discharge records from 2000 to 2010. Women with an ICD-10-AM code of M08 or M09 in the hospital records were considered to have JIA. Logistic regression was used to calculate odds ratios for pregnancy outcomes and the lack of independence in study outcomes for multiple pregnancies in the same woman was taken into account using generalized estimating equations. RESULTS: During the study period, 601,659 women had 941,496 births. Of these births, 78 births could be attributed to 50 women with JIA. Of 78 JIA pregnancies, 53 (68%) were delivered by either Caesarean section (n = 40, 51%) or instrumental delivery (n = 13, 17%); compared with other women, those with JIA had significantly higher rates of pre-eclampsia, postpartum haemorrhage and severe maternal morbidity. Compared with other infants, those with mothers with JIA were more likely to be born prematurely, but were not at increased risk of being small for gestational age, requiring neonatal intensive care, having a low Apgar score at 5 min or severe neonatal morbidity. CONCLUSION: Infants of women with JIA did not have an increased risk of adverse neonatal outcomes. Intensive obstetric care might be required during pregnancy for women with JIA given the increased risk of maternal morbidity.

Denosumab and Mortality in a Real-World Setting: A Comparative Study.

Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42-0.77; men HR = 0.56, 95% CI 0.40-0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13-1.98; men HR = 2.74; 95% CI 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).

Carpal tunnel syndrome and its relationship to occupation: a meta-analysis.

OBJECTIVE: To examine the association between work place exposure and CTS by meta-analysis, including analyses with respect to exposure to hand force, repetition, vibration and wrist posture. METHODS: All relevant peer-reviewed articles published between January 1980 and December 2009 were identified by a systematic search using the MEDLINE, CINAHL and PubMed databases. Papers were critiqued independently by two researchers and the relevant exposure information was extracted. Using the raw data of exposed and unexposed cases, a cumulative effect of specific exposure risks were calculated for hand force, repetition, a combination of force and repetition, vibration and wrist posture using the statistical program, Stata version 11 (StataCorp, College Station, TX, USA). Heterogeneity, meta-regression, publication bias and subgroup sensitivity analyses were performed. RESULTS: Thirty-seven studies from English-language literature met the inclusion criteria. Using National Institute for Occupational Health and Safety criteria for case definition, a significant positive association between CTS and hand force, repetition, use of vibratory tools and wrist posture was observed with approximate doubling of risk for all exposures. Significant heterogeneity among studies was observed for most exposures and metaregression analyses identified CTS case definition, study design, country and risk of bias score to be the significant determinants. When a more conservative definition of CTS was employed to include nerve conduction abnormality with symptoms and/or signs, risk factors significantly associated with an increased risk of CTS among exposed workers were: vibration [odds ratio (OR) 5.40; 95% CI 3.14, 9.31], hand force (OR 4.23; 95% CI 1.53, 11.68) and repetition (OR 2.26; 95% CI 1.73, 2.94). There was a non-significant trend for the association between CTS and combined exposure to both force and repetition (OR 1.85; 95% CI 0.99, 3.45) and wrist posture (OR 4.73; 95% CI 0.42, 53.32). CONCLUSION: Occupational exposure to excess vibration, increased hand force and repetition increase the risk of developing CTS. Workplace strategies to avoid overexposure to these risk factors should be implemented.

Explaining the gap in the experience of depression among arthritis patients.

OBJECTIVE: To explain the factors contributing to the gap in depression between employed arthritis patients with and without paid sick leave. METHODS: Blinder-Oaxaca decomposition analysis was used to identify factors that explain the gap in the experience of depressive symptoms among arthritis patients with paid and unpaid sick leave. Data from the 2018 National Health Interview Survey, USA, was used. RESULTS: A total of 7189 of the NHIS survey participants given the diagnosis of arthritis were identified, of which 39% were male and 61% were female, with mean age of 63.5 years. The decomposition findings suggest patients in the unpaid sick leave group were more likely to report depressive symptoms compared to patients with paid sick leave. The major contributors to the gap in the report of depressive symptoms are sex (female) and annual income (less than 35,000 USD). CONCLUSION: Findings suggest that the absence of paid sick leave is a key determinant for experiencing depressive symptoms among individuals with arthritis. The provision of paid sick leave may reduce report of depressive symptoms among employed arthritis patients in the USA. KEY POINTS: • Individuals with arthritis are consistently at greater risk of depression and unemployment as compared to individuals without arthritis. • To date greater emphasis is put on determinants of unemployment, while there is no available data on benefits associated with being employed, such as sick leave, and how it affects mental health. • Patients with unpaid sick leave appear to experience more persistent depressive symptoms than patients with access to paid sick leave. • To tackle burden of depression among arthritis patients, provision of paid sick leave may be an effective intervention.

Contribution of a common variant in the promoter of the 1-α-hydroxylase gene (CYP27B1) to fracture risk in the elderly.

CYP27B1 encodes mitochondrial 1α-hydroxylase, which converts 25-hydroxyvitamin D to its active 1,25-dihydroxylated metabolite. We tested the hypothesis that common variants in the CYP27B1 promoter are associated with fracture risk. The study was designed as a population-based genetic association study, which involved 153 men and 596 women aged 65-101 years, who had been followed for 2.2 years (range 0.1-5.5) between 1999 and 2006. During the follow-up period, the incidence of fragility fractures was ascertained. Bone ultrasound attenuation (BUA) was measured in all individuals, as were serum 25-hydroxyvitamin D and PTH concentrations; 86% subjects had vitamin D insufficiency. Genotypes were determined for the -1260C>A (rs10877012) and +2838T>C (rs4646536) CYP27B1 polymorphisms. A reporter gene assay was used to assess functional expression of the -1260C>A CYP27B1 variants. The association between genotypes and fracture risk was analyzed by Cox's proportional hazards model. We found that genotypic distribution of CYP27B1 -1260 and CYP27B1 +2838 polymorphisms was consistent with the Hardy-Weinberg equilibrium law. The two polymorphisms were in high linkage disequilibrium, with D' = 0.96 and r² = 0.94. Each C allele of the CYP27B1 -1260 polymorphism was associated with increased risk of fracture (hazard ratio = 1.34, 95% CI 1.03-1.73), after adjustment for age, sex, number of falls, and BUA. In transient transfection studies, a reporter gene downstream of the -1260(A)-containing promoter was more highly expressed than that containing the C allele. These data suggest that a common but functional variation within the CYP27B1 promoter gene is associated with fracture risk in the elderly.

Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti-apolipoprotein A-I (anti-Apo A-I), anti-high-density lipoprotein (anti-HDL), and anti-C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. METHODS: IgG anti-Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. RESULTS: Serum levels of IgG anti-Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti-Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti-Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti-Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti-double-stranded DNA. CONCLUSION: Persistent disease activity is associated with a significant increase in IgG anti-Apo A-I and anti-HDL in patients with SLE.

Should response rules be used to decide continued subsidy of very expensive drugs? A checklist for decision makers.

Response rules are increasingly used by the Pharmaceuticals Benefits Scheme (PBS) in Australia and the National Institute of Clinical Excellence (NICE) in the U.K. to limit continued subsidy of very expensive drugs to patients who demonstrate an 'adequate' response. By targeting therapy to patients who appear to benefit most, policy makers aim to increase the cost-effectiveness of therapy. However, the value of response rules in fulfilling this aim is unproven. We present a four-item checklist that may be used to help decision makers identify when a response rule is appropriate. As an example, we apply our checklist to the response rules used for tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis. On the basis of the checklist we find that the response rules in both countries are inadequate and may cause therapy to be inappropriately ceased in some and continued in others. Careful assessment is needed before decision makers adopt a response rule as a way of increasing the cost effectiveness of therapy.

BMI: a simple, rapid and clinically meaningful index of under-nutrition in the oldest old?

BMI is commonly used as a sole indicator for the assessment of nutritional status. While it is a good predictor of morbidity and mortality among young and middle-aged adults, its predictive ability among the oldest old remains unclear. The objective of the present study was to investigate the relationship between BMI and risk of falls, fractures and all-cause mortality among older Australians in residential aged care facilities. One thousand eight hundred and forty-six residents of fifty-two nursing homes and thirty hostels in northern Sydney, Australia, participated in the present study. Baseline weight and height were measured and BMI (kg/m2) calculated. For 2 years following the baseline measurements, incidence and date of all falls and fractures were recorded by research nurses who visited the facilities regularly and date of death was documented based on the participants' records at each facility. Cox proportional hazards regression models were calculated to determine the relationship between baseline BMI and time to fall, fracture or death, within 2 years following the baseline measures taken to be the censoring date. After adjustments were made for age, sex and level of care, low BMI (,22 kg/m2) increased the risk of fracture by 38% (hazard ratio = 1.38, 95% CI 1.11, 1.73) and all-cause mortality by 52% (hazard ratio = 1.52, 95% CI 1.30, 1.79). The magnitude of this effect was only slightly reduced when adjustments were further made to incorporate cognition, number of medications, falls and fracture in the subsequent 2-year period. In conclusion, BMI has predictive ability in the area of fracture and all-cause mortality for residents of aged care facilities. It is a simple and rapid indicator of nutritional status rendering it a useful nutrition screen and goal for nutrition intervention.

Risk factors for hip fracture among institutionalised older people.

BACKGROUND: risk factors for hip fracture in community-dwelling individuals have been extensively studied, but there have been fewer studies of institutionalised older people. METHODS: a total of 1,894 older people (1,433 females, 461 males; mean age 86 years, SD 7.1 years) were recruited from 52 nursing homes and 30 intermediate-care nursing care facilities in Australia during March 1999 and February 2003. We assessed clinical risk factors for hip fracture and skeletal fragility by calcaneus broadband ultrasound attenuation (BUA) at baseline and then followed up for fracture for 4 years. Hip fractures were validated by x-ray reports. Survival analysis with age as a time-dependent covariate was used to analyse the data. RESULTS: during a mean follow-up period of 2.65 years (SD 1.38), 201 hip fractures in 191 residents were recorded, giving an overall hip fracture incidence rate of 4.0% per person year (males 3.6% and females 4.1%). Residents living in intermediate-care hostels had a higher crude hip fracture rate (4.6% vs. 3.0%) than those living in high-care nursing homes. In multivariate analysis, an increased risk of hip fracture was significantly associated with older age, cognitive impairment, a history of fracture since age 50, lower body weight, longer lower leg length and poorer balance in intermediate-care hostel residents, but not with lower BUA. CONCLUSIONS: institutionalised older people, who are at a higher risk of hip fracture than community-dwelling individuals, have differences in some risk factors for hip fracture that should be considered in targeting intervention programs.

Instrument Selection Using the OMERACT Filter 2.1: The OMERACT Methodology.

OBJECTIVE: Outcome Measures in Rheumatology (OMERACT) Filter 2.1 revised the process used for core outcome measurement set selection to add rigor and transparency in decision making. This paper describes OMERACT's methodology for instrument selection. METHODS: We presented instrument selection processes, tools, and reporting templates at OMERACT 2018, introducing the concept of "3 pillars, 4 questions, 7 measurement properties, 1 answer." Truth, discrimination, and feasibility are the 3 original OMERACT pillars. Based on these, we developed 4 signaling questions. We introduced the Summary of Measurement Properties table that summarizes the 7 measurement properties: truth (domain match, construct validity), discrimination [test-retest reliability, longitudinal construct validity (responsiveness), clinical trial discrimination, thresholds of meaning], and feasibility. These properties address a set of standards which, when met, answer the one question: Is there enough evidence to support the use of this instrument in clinical research of the benefits and harms of treatments in the population and study setting described? The OMERACT Filter 2.1 was piloted on 2 instruments by the Psoriatic Arthritis Working Group. RESULTS: The methodology was reviewed in a full plenary session and facilitated breakout groups. Tools to facilitate retention of the process (i.e., "The OMERACT Way") were provided. The 2 instruments were presented, and the recommendation of the working group was endorsed in the first OMERACT Filter 2.1 Instrument Selection votes. CONCLUSION: Instrument selection using OMERACT Filter 2.1 is feasible and is now being implemented.

Uptake of the OMERACT-OARSI Hip and Knee Osteoarthritis Core Outcome Set: Review of Randomized Controlled Trials from 1997 to 2017.

OBJECTIVE: To assess the uptake of the OMERACT-OARSI (Outcome Measures in Rheumatology- Osteoarthritis Research Society International) core outcome set (COS) domains in hip and/or knee osteoarthritis (OA) trials. METHODS: There were 382 trials of hip and/or knee OA identified from the ClinicalTrial.gov registry from 1997 to 2017. Frequency of COS adoption was assessed by year and per 5-yearly phases. RESULTS: COS adoption decreased from 61% between 1997 and 2001 to 38% between 2012 and 2016. Pain (95%) and physical function (86%) were most consistently adopted. Patient's global assessment (48%) was the principal missing domain. CONCLUSION: Limited adoption of the COS domains indicates that further consideration to improve uptake is required.

The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis.

OBJECTIVE: To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA). METHODS: An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary. RESULTS: Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient's global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention. CONCLUSION: The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain.

Fracture risk assessment in frail older people using clinical risk factors.

BACKGROUND: this study aims to develop and evaluate a simple fracture risk index for use in frail older people. METHODS: clinical risk factors were assessed at baseline for 2,005 older people (473 males, 1,532 females; mean age 85.7 years, SD 7.1 years) living in aged-care facilities. Fractures were ascertained for 2 years from baseline. Cox regression model was used to identify significant risk factors for fracture. Hazard ratios (HRs) from the model were assigned as weights. The risk index was calculated by multiplying the weights of all risk factors. RESULTS: during a mean follow-up of 1.64 years, 401 fractures occurred in 338 participants. Significant independent clinical risk factors for fracture were institution type, balance, history of previous fracture, cognitive function, number of medications, weight and lower leg length (n = 1,813). The index was capable of identifying higher-risk individuals, with almost an 8-fold increase in the risk of fracture for residents from the lowest 15% to the highest 18% of the score. Among 1-year survivors, a high score (>or=15) indicated approximately a one-in-six chance of fracture, while a low score (<8) indicated only a one-in-forty chance of fracture within a year. The area under the receiver operating characteristic (ROC) curve was 0.69 (95% CI: 0.65-0.72) and 0.68 (95% CI: 0.65-0.71) for identifying someone who would have a fracture in 1 and 2 years respectively. CONCLUSIONS: this risk index could identify individuals at higher fracture risk among institutionalised older people, and thus, could help to rationalise the provision of fracture prevention programs in this population.