Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study.

OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.

Association Between Hyperuricemia and Ultrasound-Detected Hand Synovitis.

OBJECTIVE: Although hand synovitis is prevalent in the older population, the etiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate level >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both gray-scale synovitis and the Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand gray-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex, and body mass index. RESULTS: All required assessments for analysis were available for 3,286 participants. The prevalence of hand gray-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI] 1.00-1.62). Participants with hyperuricemia also had a higher prevalence of PDS (aOR 2.36; 95% CI 1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with the presence of gray-scale synovitis (aOR 1.27; 95% CI 1.00-1.60 and adjusted prevalence ratio [aPR] 1.26; 95% CI 1.10-1.44, respectively) and PDS (aOR 2.35; 95% CI 1.15-4.79 and aPR 2.34; 95% CI 1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidence for a positive association between hyperuricemia and prevalent hand synovitis.

Dual-energy X-ray absorptiometry derived knee shape may provide a useful imaging biomarker for predicting total knee replacement: Findings from a study of 37,843 people in UK Biobank.

Objective: We aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors. Methods: Using a 129-point statistical shape model, knee shape (expressed as a B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of images and an overall score was assigned. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with TKR risk, adjusting for age, sex, height and weight. Results: The analysis included 37,843 individuals (mean age 63.7 years). In adjusted models, B-score was associated with TKR: each unit increase in B-score, reflecting one standard deviation from the mean healthy shape, corresponded to a hazard ratio (HR) of 2.25 (2.08, 2.43), while a lower mJSW had a HR of 2.28 (1.88, 2.77). Among the 6719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In ROC analyses, a model combining B-score, osteophyte score, and demographics outperformed a model including demographics alone (AUC â€‹= â€‹0.87 vs 0.73). Conclusions: Using statistical shape modelling, we derived a DXA-based imaging biomarker for knee shape that was associated with kOA progression. When combined with osteophytes and demographic data, this biomarker may help identify individuals at high risk of TKR, facilitating targeted interventions.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (ß = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

Healthcare utilisation and mortality in people with osteoarthritis in the UK: findings from a national primary care database.

BACKGROUND: The burden of osteoarthritis (OA) in UK primary care has not been investigated thoroughly. AIM: To estimate healthcare use and mortality in people with OA (overall and joint specific). DESIGN AND SETTING: A matched cohort study of adults with an incident diagnosis of OA in primary care were selected for the study using UK national Clinical Practice Research Datalink (CPRD) electronic records. METHOD: Healthcare utilisation was measured as the annual average number of primary care consultations and admissions to hospital after the index date for any cause and all-cause mortality data in 221 807 people with OA and an equal number of controls (with no OA diagnosis) who were matched to the case patients by age (standard deviation 2 years), sex, practice, and year of registration. The associations between OA and healthcare utilisation and all-cause mortality were estimated using multinomial logistic regression and Cox regression, respectively, adjusting for covariates. RESULTS: The mean age of the study population was 61 years and 58% were female. In the OA group, the median number of primary care consultations per year after the index date was 10.91 compared with 9.43 in the non-OA control group (P = 0.001) OA was associated with an increased risk of GP consultation and admission to hospital. The adjusted hazard ratio for all-cause mortality was 1.89 (95% confidence interval [CI] = 1.85 to 1.93) for any OA, 2.09 (95% CI = 2.01 to 2.19) for knee OA, 2.08 (95% CI = 1.95 to 2.21) for hip OA, and 1.80 (95% CI = 1.58 to 2.06) for wrist/hand OA, compared with the respective non-OA control group. CONCLUSION: People with OA had increased rates of GP consultations, admissions to hospital, and all-cause mortality that varied across joint sites.

Prevalence and distribution of ultrasound-detected hand synovial abnormalities in a middle-aged and older population.

OBJECTIVE: Synovial abnormalities are modifiable targets for hand pain and osteoarthritis. We examined the prevalence and distribution of ultrasound-detected hand synovial abnormalities in a community-derived sample of older people in China. METHODS: Within the Xiangya Osteoarthritis Study, a community-based study, we assessed synovial hypertrophy (SH), joint effusion, and Power Doppler signal (PDS) on all fingers and thumbs of both hands using standardized ultrasound examinations (score: 0-3). We assessed distribution patterns of SH and effusion using χ2-test and interrelationships of SH and effusion in different joints and hands by generalized estimating equations. RESULTS: Among 3,623 participants (mean age: 64.4 years; women: 58.1%), prevalence of SH, effusion and PDS were 85.5%, 87.3% and 1.5%, respectively. Prevalence of SH, effusion and PDS increased with age, was higher in the right hand than in the left hand and was more common in proximal than in distal hand joints. SH and effusion often occurred in multiple joints (P < 0.001). SH in one joint was strongly associated with presence of SH in the same joint of the opposite hand (odds ratio [OR]= 6.60, 95% confidence interval [CI]: 6.19-7.03) followed by SH in other joints in the same row, (OR=5.70, 95%CI: 5.32-6.11), and then other joints in the same ray of the same hand (OR=1.49, 95%CI: 1.39-1.60). Similar patterns were observed for effusion. CONCLUSION: Hand synovial abnormalities are common among older people, often affect multiple hand joints and present a unique pattern. These findings suggest both systemic and mechanical factors play roles in their occurrence.

Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials.

OBJECTIVE: Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown. DESIGN: Network meta-analysis. DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA. RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs). CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.

Comorbidities and use of analgesics in people with knee pain: a study in the Nottingham Knee Pain and Health in the Community (KPIC) cohort.

Objectives: The aims were to examine the prevalence of comorbidities and role of oral analgesic use in people with knee pain (KP) compared with those without. Methods: The Knee Pain and related health In the Community (KPIC) cohort comprises community-derived adults aged ≥40 years, irrespective of knee pain. Thirty-six comorbidities across 10 systems were compared between people with KP and controls without KP or knee OA. Multivariable logistic regression analysis was used to determine the adjusted odds ratio (aOR) and 95% CI for multimorbidity (at least two chronic conditions) and each specific comorbidity. Both prescribed and over-the-counter analgesics were included in the model, and their interactions with KP for comorbidity outcomes were examined. Results: Two thousand eight hundred and thirty-two cases with KP and 2518 controls were selected from 9506 baseline participants. The mean age of KP cases was 62.2 years, and 57% were women. Overall, 29% of the total study population had multimorbidity (KP cases 34.4%; controls 23.8%). After adjustment for age, sex, BMI and analgesic use, KP was significantly associated with multimorbidity (aOR 1.35; 95% CI 1.17, 1.56) and with cardiovascular (aOR 1.25; 95% CI 1.08, 1.44), gastrointestinal (aOR 1.34; 95% CI 1.04, 1.92), chronic widespread pain (aOR 1.54; 95% CI 1.29, 1.86) and neurological (aOR 1.32; 95% CI 1.01, 1.76) comorbidities. For multimorbidity, the use of paracetamol and opioids interacted positively with KP, whereas the use of NSAIDs interacted negatively for seven comorbidities. Conclusion: People with KP are more likely to have other chronic conditions. The long-term benefits and harms of this change remain to be investigated. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02098070.

Comorbidities in osteoarthritis (ComOA): a combined cross-sectional, case-control and cohort study using large electronic health records in four European countries.

INTRODUCTION: Osteoarthritis (OA) is one of the leading chronic conditions in the older population. People with OA are more likely to have one or more other chronic conditions than those without. However, the temporal associations, clusters of the comorbidities, role of analgesics and the causality and variation between populations are yet to be investigated. This paper describes the protocol of a multinational study in four European countries (UK, Netherlands, Sweden and Spain) exploring comorbidities in people with OA. METHODS AND ANALYSIS: This multinational study will investigate (1) the temporal associations of 61 identified comorbidities with OA, (2) the clusters and trajectories of comorbidities in people with OA, (3) the role of analgesics on incidence of comorbidities in people with OA, (4) the potential biomarkers and causality between OA and the comorbidities, and (5) variations between countries.A combined case-control and cohort study will be conducted to find the temporal association of OA with the comorbidities using the national or regional health databases. Latent class analysis will be performed to identify the clusters at baseline and joint latent class analysis will be used to examine trajectories during the follow-up. A cohort study will be undertaken to evaluate the role of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol on the incidence of comorbidities. Mendelian randomisation will be performed to investigate the potential biomarkers for causality between OA and the comorbidities using the UK Biobank and the Rotterdam Study databases. Finally, a meta-analyses will be used to examine the variations and pool the results from different countries. ETHICS AND DISSEMINATION: Research ethics was obtained according to each database requirement. Results will be disseminated through the FOREUM website, scientific meetings, publications and in partnership with patient organisations.

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.

Prevalence of ultrasound-detected knee synovial abnormalities in a middle-aged and older general population-the Xiangya Osteoarthritis Study.

BACKGROUND: There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample. METHODS: Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA. RESULTS: There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval [CI] 2.00-2.86) for synovial hypertrophy, 1.58 (95%CI 1.39-1.80) for effusion, and 4.36 (95%CI 3.09-6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38-4.82), 2.01 (95%CI 1.76-2.29), and 6.49 (95%CI 4.51-9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding P for interaction were 0.004 and 0.067, respectively. CONCLUSIONS: Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.

Temporal relationship between osteoarthritis and comorbidities: a combined case control and cohort study in the UK primary care setting.

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.

Constitutional morphological features and risk of hip osteoarthritis: a case-control study using standard radiographs.

OBJECTIVES: To evaluate the risk of association with hip osteoarthritis (OA) of 14 morphological features measured on standard antero-posterior pelvis radiographs. METHODS: A case-control study of 566 symptomatic unilateral hip OA cases and 1108 controls without hip OA, using the Genetics of OA and Lifestyle database. Unaffected hips of cases were assumed to reflect pre-OA morphology of the contralateral affected hip. ORs with 95% CI adjusted for confounding factors were calculated using logistic regression. Hierarchical clustering on principal component method was used to identify clusters of morphological features. Proportional risk contribution (PRC) of these morphological features in the context of other risk factors of hip OA was estimated using receiver operating characteristic analysis. RESULTS: All morphological features showed right-left symmetry in controls. Each feature was associated with hip OA after adjusting for age, gender and body mass index. Increased sourcil angle had the strongest association (OR: 6.93, 95% CI 5.16 to 9.32). Three clusters were identified. The PRC varied between individual features, as well as between clusters. It was 35% (95% CI 31% to 40%) for all 14 morphological features, compared to 21% (95% CI 19% to 24%) for all other well-established risk factors. CONCLUSIONS: Constitutional morphological variation strongly associates with hip OA development and may explain much of its heritability. Relevant morphological measures can be assessed readily on standard radiographs to help predict risk of hip OA. Prospective studies are required to provide further support for causality.

Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials.

OBJECTIVES: To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. METHODS: Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0-10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. RESULTS: A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. CONCLUSION: Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT03146689.

Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study.

OBJECTIVE: Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA. METHODS: This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity. RESULTS: A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01). CONCLUSION: Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.

Comorbidities in Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Osteoarthritis (OA) is a common chronic condition in older individuals, but its association with other chronic conditions is largely unknown. This study aimed to systematically review the literature on comorbidities in individuals with OA compared to those without. METHODS: We searched 4 databases for observational studies on comorbidities in individuals with OA. Studies of OA only or in comparison with non-OA controls were included. The risk of bias and study quality were assessed using the Newcastle-Ottawa Scale. The prevalence of comorbidities in the OA group and the prevalence ratio (PR) and 95% confidence interval (95% CI) between OA and non-OA groups were calculated. RESULTS: In all, 42 studies from 16 countries (27 case-only and 15 comparative studies) met the inclusion criteria. The mean age of participants varied from 51 to 76 years. The pooled prevalence of any comorbidity was 67% (95% CI 57-74) in individuals with OA versus 56% (95% CI 44-68) in individuals without OA. The pooled PR for any comorbidity was 1.21 (95% CI 1.02-1.45). The PR increased from 0.73 (95% CI 0.43-1.25) for 1 comorbidity to 1.58 (95% CI 1.03-2.42) for 2, and to 1.94 (95% CI 1.45-2.59) for ≥3 comorbidities. The key comorbidities associated with OA were stroke (PR 2.61 [95% CI 2.13-3.21]), peptic ulcer (PR 2.36 [95% CI 1.71-3.27]), and metabolic syndrome (PR 1.94 [95% CI 1.21-3.12]). CONCLUSION: Individuals with OA are more likely to have other chronic conditions. The association is dose-dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.