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Objectives: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster., Methods: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards., Results: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15])., Conclusion: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Joint replacement due to end-stage OA has been linked to incidence of several cancers. We aimed to estimate the association between newly diagnosed knee and hip OA and incidence of nine common cancer types., Methods: We identified persons with incident knee or hip OA, aged ≥40 years, between 2009 and 2015 in the SIDIAP database in Catalonia, Spain. We matched up to three OA-free controls on age, sex and general practitioner. We followed participants from 1 year after OA diagnosis until migration, death, end of study at 31 December 2017 or incident cancer of: stomach, colorectal, liver, pancreas, lung, skin, breast, prostate and bladder. We used flexible parametric survival models, adjusted for confounders. Estimates were corrected for misclassification using probabilistic bias analysis., Results: We included 117 750 persons with knee OA and matched 309 913 persons without, with mean (s.d.) age of 67.5 (11.1) years and 63% women. The hip cohort consisted of 39 133 persons with hip OA and 116 713 controls. For most of the included cancers, the hazard ratios (HRs) were close to 1. The HR of lung cancer for knee OA exposure was 0.80 (95% CI: 0.71, 0.89) and attenuated to 0.98 (0.76, 1.27) in non-smokers. The hazard of colorectal cancer was lower in persons with both knee and hip OA by 10-20%., Conclusions: Knee and hip OA are not associated with studied incident cancers, apart from lower risk of colorectal cancer. The often-reported protective association of knee OA with lung cancer is explained by residual confounding., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza., Methods: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization., Results: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%)., Conclusion: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Better indicators from affordable, sustainable data sources are needed to monitor population burden of musculoskeletal conditions. We propose five indicators of musculoskeletal health and assessed if routinely available primary care electronic health records (EHR) can estimate population levels in musculoskeletal consulters., Methods: We collected validated patient-reported measures of pain experience, function and health status through a local survey of adults (≥35 years) presenting to English general practices over 12 months for low back pain, shoulder pain, osteoarthritis and other regional musculoskeletal disorders. Using EHR data we derived and validated models for estimating population levels of five self-reported indicators: prevalence of high impact chronic pain, overall musculoskeletal health (based on Musculoskeletal Health Questionnaire), quality of life (based on EuroQoL health utility measure), and prevalence of moderate-to-severe low back pain and moderate-to-severe shoulder pain. We applied models to a national EHR database (Clinical Practice Research Datalink) to obtain national estimates of each indicator for three successive years., Results: The optimal models included recorded demographics, deprivation, consultation frequency, analgesic and antidepressant prescriptions, and multimorbidity. Applying models to national EHR, we estimated that 31.9% of adults (≥35 years) presenting with non-inflammatory musculoskeletal disorders in England in 2016/17 experienced high impact chronic pain. Estimated population health levels were worse in women, older aged and those in the most deprived neighbourhoods, and changed little over 3 years., Conclusion: National and subnational estimates for a range of subjective indicators of non-inflammatory musculoskeletal health conditions can be obtained using information from routine electronic health records., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To determine the burden of comorbidities in OA and their temporal relationships in the UK., Methods: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify people with incident OA and age, gender and practice matched non-OA controls from UK primary care. Controls were assigned the same index date as matched cases (date of OA diagnosis). Associations between OA and 49 individual comorbidities and multimorbidities (two or more comorbidities excluding OA) both before and after OA diagnosis were estimated, adjusting for covariates, using odds ratios (aORs) and hazard ratios (aHRs), respectively., Results: During 1997-2017, we identified 221 807 incident OA cases and 221 807 matched controls. Of 49 comorbidities examined, 38 were associated with OA both prior to and following the diagnosis of OA and 2 (dementia and systemic lupus erythematosus) were associated with OA only following the diagnosis of OA. People with OA had a higher risk of developing heart failure [aHR 1.63 (95% CI 1.56, 1.71)], dementia [aHR 1.62 (95% CI 1.56, 1.68)], liver diseases [aHR 1.51 (95% CI 1.37, 1.67)], irritable bowel syndrome [aHR 1.51 (95% CI 1.45, 1.58)], gastrointestinal bleeding [aHR 1.49 (95% CI 1.39, 1.59)], 10 musculoskeletal conditions and 25 other conditions following OA diagnosis. The aOR for multimorbidity prior to the index date was 1.71 (95% CI 1.69, 1.74), whereas the aHR for multimorbidity after the index date was 1.29 (95% CI 1.28, 1.30)., Conclusions: People with OA are more likely to have other chronic conditions both before and after the OA diagnosis. Further study on shared aetiology and causality of these associations is needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls., Methods: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995-2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD)., Results: There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population., Conclusion: We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Intra-articular steroid injection is commonly used to treat base of thumb osteoarthritis (BTOA), despite a lack of large-scale data on safety and effectiveness. We estimate the incidence of serious complications and further procedures following BTOA injection, including the risk of post-operative serious surgical site infection for subsequent operative intervention., Methods: Hospital Episode Statistics data linked to mortality records from 1 April 1998 to 31 March 2017 were used to identify all BTOA injections undertaken in adults in the National Health Service secondary care in England. Patients were followed up longitudinally until death or 31 March 2017. A multivariable regression with a Fine and Gray model adjusting for the competing risk of mortality in addition to age, sex and socioeconomic deprivation was used to identify factors associated with progression to further procedure. Secondary outcomes included serious complications after injection and subsequent surgical site infection., Results: A total of 19 120 primary injections were performed during the 19-year period in 18 356 patients. Of these 76.5% were female; mean age 62 years (s.d. 10.6); 50.48% underwent further procedure; 22.40% underwent surgery. Median time to further intervention was 412 days (IQR 110-1945). Female sex was associated with increased risk of proceeding to surgery. Serious complication rate following injection was 0.04% (0.01-0.08) within 90 days. Of those proceeding to surgery 0.16% (0.06-0.34) presented with a wound infection within 30 days and 90 days, compared with an overall post-operative wound infection rate of 0.03% (0.02-0.05)., Conclusions: Very low rates of serious complications were identified following BTOA injections performed in secondary care; only one in five patients proceeded to subsequent surgery., Clinical Trial Registration: clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03573765., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA., Methods: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%., Results: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis., Conclusion: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation., Trial Registration: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To estimate the lifetime risk of knee and hip replacement following a diagnosis of RA., Methods: The analysis was undertaken using routinely collected data from the English NHS. Diagnosis of RA was identified using primary care records, with knee and hip replacement observed in linked hospital records. Parametric survival models were fitted for up to 15 years of follow-up, with age, sex, Charlson comorbidity score, socioeconomic status, BMI and smoking status included as explanatory variables. A decision model was used to combine and extrapolate survival models to estimate lifetime risk., Results: The number of individuals with a diagnosis of RA and included in the study was 13 961. Lifetime risk of knee replacement and hip replacement was estimated to be 22% (95% CI: 16, 29%) and 17% (95% CI: 11, 26%) following a diagnosis of RA for the average patient profile (non-smoking women aged 64 with no other comorbidities, BMI of 27 and in the top socioeconomic quintile). Risks were higher for younger patients., Conclusion: The lifetime risk of knee and hip replacement for individuals with a diagnosis of RA is approximately double that of the general population. These findings allow for a better understanding of long-term prognosis and healthcare resource use, and highlight the importance of timely diagnosis and effective treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement., Methods: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed., Results: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement., Conclusion: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To compare outcomes of total knee replacement (TKR) and total hip replacement (THR) for individuals with RA and OA., Methods: We performed a cohort study using routinely collected data. Oxford Knee Score, Oxford Hip Score, and EuroQol 5-dimension 3-level (EQ-5D-3L) questionnaires were collected before and 6 months after surgery. Multivariable regressions were used to estimate the association between diagnosis and post-operative scores after controlling for pre-operative scores and patient characteristics., Results: Study cohorts included 2070 OA and 142 RA patients for TKR and 2030 OA and 98 RA patients for THR. Following TKR, the median Oxford Knee Score was 37 [interquartile range (IQR) 29-43] for OA and 36 (27-42) for RA while the median EQ-5D-3L was 0.76 (0.69-1.00) and 0.69 (0.52-0.85), respectively. After THR, the Oxford Hip Score was 42 (IQR 36-46) for OA and 39 (30-44) for RA while the EQ-5D-3L was 0.85 (0.69-1.00) and 0.69 (0.52-1.00), respectively. The estimated effect of RA, relative to OA, on post-operative scores was -0.05 (95% CI -1.57, 1.48) for the Oxford Knee Score, -0.09 (-0.13, -0.06) for the EQ-5D-3L following TKR, -1.35 (-2.93, -0.22) for the Oxford Hip Score, and -0.08 (-0.12, -0.03) for the EQ-5D-3L following THR., Conclusion: TKR and THR led to substantial improvements in joint-specific scores and overall quality of life. While diagnosis had no clinically meaningful effect on joint-specific outcomes, improvements in general quality of life were somewhat less for those with RA, which is likely due to the systemic and multijoint nature of rheumatoid disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate temporal trends in the incidence and prevalence of gout in the adult Danish population., Methods: Using the nationwide Danish National Patient Registry, we calculated the number of incident gout patients (per 100 000 person-years) within each 1 year period from 1995 to 2015 and the prevalence of gout in 2000 and 2015. Further, we calculated age- and gender-specific incidence rates of gout from 1995 to 2015., Results: We identified a total of 45 685 incident gout patients (72.9% males) with a mean age of 65 years (s.d. 16) at diagnosis. In both genders, an increase in age-standardized incidence rates was observed from 32.3/100 000 (95% CI 30.7, 33.9) in 1995 to 57.5/100 000 (95% CI 55.6, 59.5) in 2015 (P < 0.001). Similar trends were observed for 8950 cases diagnosed in rheumatology departments. We likewise observed an increase in the prevalence of gout from 0.29% (95% CI 0.29, 0.30) in 2000 to 0.68% (95% CI 0.68, 0.69) in 2015., Conclusions: The annual incidence rate of gout increased by almost 80% in Denmark between 1995 and 2015. The prevalence increased by nearly 130% between 2000 and 2015. Reasons for this are unknown but may include an increase in risk factors (e.g. obesity, diabetes mellitus), longer life expectancy and increased awareness of the disease among patients and/or health professionals., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine recent trends in the rate and management of new cases of OA presenting to primary healthcare using UK nationally representative data., Methods: Using the Clinical Practice Research Datalink we identified new cases of diagnosed OA and clinical OA (including OA-relevant peripheral joint pain in those aged over 45 years) using established code lists. For both definitions we estimated annual incidence density using exact person-time, and undertook descriptive analysis and age-period-cohort modelling. Demographic characteristics and management were described for incident cases in each calendar year. Sensitivity analyses explored the robustness of the findings to key assumptions., Results: Between 1992 and 2013 the annual age-sex standardized incidence rate for clinical OA increased from 29.2 to 40.5/1000 person-years. After controlling for period effects, the consultation incidence of clinical OA was higher for successive cohorts born after the mid-1950s, particularly women. In contrast, with the exception of hand OA, we observed no increase in the incidence of diagnosed OA: 8.6/1000 person-years in 2004 down to 6.3 in 2013. In 2013, 16.4% of clinical OA cases had an X-ray referral. While NSAID prescriptions fell from 2004, the proportion prescribed opioid analgesia rose markedly (0.1% of diagnosed OA in 1992 to 1.9% in 2013)., Conclusion: Rising rates of clinical OA, continued use of plain radiography and a shift towards opioid analgesic prescription are concerning. Our findings support the search for policies to tackle this common problem that promote joint pain prevention while avoiding excessive and inappropriate health care., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To assess whether publication of national treatment guidelines improved the management of early RA in the UK., Methods: Incident diagnoses of RA in persons aged over 18 years from 1995 to 2010 were identified from the Clinical Practice Research Datalink. Using a natural experimental study design, interrupted time series analysis was used to assess whether trends in the proportion of patients receiving DMARDs, within 3 and 12 months of diagnosis, changed following publication of British Society for Rheumatology guidelines in 2006., Results: Between 1995 and 2010, 11 772 incident cases of RA were identified. There was a progressive increase in the proportion of patients prescribed any DMARD within 12 months from 43.3% in 1995 to 78.5% in 2010. After publication of the British Society for Rheumatology guidelines, the proportion of patients prescribed any DMARD within 12 months increased by 4.2% (P = 0.053). Prior to the guidance, prescribing was increasing by 1.64% per year, compared with 3.55% per year after publication (P < 0.001)., Conclusion: Guidelines published by a national body can improve the proportion of patients receiving DMARD treatment in the first year after diagnosis of RA., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Patients with OA use different drugs in their search for relief. We aimed to study the prevalence of use and combinations of different medications for OA in a population-based cohort of OA patients in Catalonia, Spain, while characterizing users of each of the drugs available, with a particular focus on cardiovascular risk factors., Methods: Data were obtained from the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) database, which includes electronic medical records and pharmacy invoice data for >5 million people from Catalonia. Study participants were those with a clinical diagnosis of OA in 2006-10. Drugs studied included oral and topical NSAIDs, analgesics (paracetamol, metamizole), opioids (tramadol, fentanyl), cyclooxygenase 2 (COX-2) inhibitors and symptomatic slow-acting drugs in OA. Drug utilization was described using medication possession ratios (MPRs), equivalent to the proportion of days covered with the drug of interest. The annual incidence of new users in the first year after OA diagnosis from 2006 to 2010 was estimated for all studied drugs among newly diagnosed OA patients using Poisson regression., Results: We identified 238 536 study participants. The most common regimen of treatment consisted of at least three drugs (53.9% of patients). The drugs most frequently used regularly (MPR ≥50%) were chondroitin (21.2%), glucosamine (15.8%) and oral NSAIDs (14.4%). The incidence of the use of opioids, COX-2 inhibitors and chondroitin increased over the 5 year period, whereas all others decreased., Conclusion: Drug combinations are common in the treatment of OA patients, who are thus exposed to potential drug interactions, with unknown impacts on their health. The increasing use of opioids and COX-2 inhibitors is noteworthy because of the potential impact on safety and costs., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)