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Background Joint replacement surgery has revolutionised the management of degenerative joint disease. Increasing demand for surgery and post-surgical reviews has overwhelmed orthopaedic services and, consequently, many centres have reduced or stopped follow-up. Such disinvestment is without an evidence base and raises questions regarding the consequences to patients. Objectives To produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Our research question was ‘Is it safe to disinvest in mid- to late-term follow-up of hip and knee replacement?’. Methods The study comprised three complementary evidence synthesis work packages to inform a final consensus process. Work package 1 was a systematic review of the clinical effectiveness and cost-effectiveness literature. Work package 2 used routine national data sets (i.e. the Clinical Practice Research Datalink–Hospital Episode Statistics, Hospital Episode Statistics–National Joint Registry–patient-reported outcome measures) to identify pre, peri and postoperative predictors of mid- to late-term revision, and prospective data from 560 patients to understand how patients present for revision surgery. Work package 3 used a Markov model to simulate the survival, health-related quality of life and NHS costs of patients following hip or knee replacement surgery. Finally, evidence from work packages 1–3 informed a face-to-face consensus panel, which involved 32 stakeholders. Results Our overarching statements are as follows: (1) these recommendations apply to post primary hip and knee replacement follow-up; (2) the 10-year time point in these recommendations is based on a lack of robust evidence beyond 10 years; and (3) in these recommendations, the term ‘complex cases’ refers to individual patient and surgical factors that may increase the risk of replacement failure. Our recommendations are as follows: for Orthopaedic Data Evaluation Panel 10A* (ODEP-10A*) minimum implants, it is safe to disinvest in routine follow-up from 1 to 10 years post non-complex hip and knee replacement provided that there is rapid access to orthopaedic review; (2) for ODEP-10A* minimum implants in complex cases or non-ODEP-10A* minimum implants, periodic follow-up post hip and knee replacement may be required from 1 to 10 years; (3) at 10 years post hip and knee replacement, clinical and radiographic evaluation is recommended; and (4) after 10 years post hip and knee replacement, frequency of further follow-up should be based on the 10-year assessment (note that ongoing rapid access to orthopaedic review is still required) [Stone M, Smith L, Kingsbury S, Czoski-Murray C, Judge A, Pinedo-Villanueva R, et al. Evidence-based follow-up recommendations following primary hip and knee arthroplasty (UK SAFE). Orthop Proc 2020;102–B:13. https://doi.org/10.1302/1358-992X.2020.5.013]. Limitations The current absence of data beyond 10 years restricted the evidence base. Conclusions For ODEP-10A* prostheses, the UK SAFE programme demonstrated that it is safe to disinvest in routine follow-up in the 1- to 10-year period after non-complex hip and knee replacement. At 10 years, clinical and radiographic review is recommended. Complex cases, implants not meeting the 10A* criteria and follow-up after revision surgery are not covered by this recommendation. Future work The evidence base for follow-up after 10 years requires further evaluation. Further work should establish the most clinically effective and cost-effective model of delivering a rapid access service and evaluate alternative models for follow-up services, such as virtual clinics. Finally, the needs and outcomes of patients who are symptomatic but do not have appropriate follow-up should be investigated. Study registration This study is registered as PROSPERO CRD42017053017. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 16. See the NIHR Journals Library website for further project information.

ObjectivesTo define the population prevalence of rotator cuff tears and test their association with pain and function loss; determine if severity symptom correlates with tear stage severity, and quantify the impact of symptomatic rotator cuff tears on primary healthcare services in a general population cohort of women.DesignCross-sectional observational study.ParticipantsIndividuals were part of the Chingford 1000 Women cohort, a 20-year-old longitudinal population study comprising 1003 women aged between 64 and 87, and representative of the population of the UK.Main outcome measuresRotator cuff pathology prevalence on ultrasound, shoulder symptoms using the Oxford Shoulder Score and resultant number of general practitioner (GP) consultations.ResultsThe population prevalence of full-thickness tears was 22.2%, which increased with age (p=0.004) and whether it was the dominant arm (Relative Risk 1.64, OR 1.58, 95% CI 1.07 to 2.33, p=0.021).Although 48.4% of full-thickness tears were asymptomatic, there was an association between rotator cuff tears and patient-reported symptoms. Individuals with at least one full-thickness tear were 1.97 times more likely than those with bilateral normal tendons (OR 3.53, 95% CI 2.00 to 5.61, p2.5 cm (p=0.009).In the cohort, 8.9% had seen their GP with shoulder pain and a full-thickness rotator cuff tear, 18.8% with shoulder pain and an abnormality and 29.3% with shoulder pain.ConclusionRotator cuff tears are common, and primary care services are heavily impacted. As 50% of tears remain asymptomatic, future research may investigate the cause of pain and whether different treatment modalities, aside from addressing the pathology, need further investigation.

Background Baseball has specific sport and positional demands that may modify joint pain compared with other sports. Persistent joint pain reduces function and is an underlying reason for seeking medical care. The pain and functional status of players after they stop competitive play are unknown. Such knowledge can assist clinicians in creating personalized physical examinations and interventions for baseball players as they transition to retirement. The purpose of this study was to (1) evaluate persistent joint pain and arm function in former baseball players and (2) determine whether playing position is associated with increased odds of joint pain and reduced arm function in former baseball players. Methods A cross-sectional survey was performed. Eligibility criteria consisted of (1) played ≥1 collegiate baseball season, (2) aged ≥18 years, and (3) formerly played baseball (currently retired). Outcomes assessed included persistent joint pain and Single Assessment Numeric Evaluation (SANE). Explanatory variables included playing position (position, two-way, or pitcher). Multivariable logistic and linear regressions were performed. Models were adjusted for age, body mass index, arm dominance, playing standard, years played baseball, and injury and surgery history. Results A total of 117 former baseball players participated (age: 36.8 [13.7] years). The mean dominant SANE score was 70.2 (standard deviation 24.1), and the mean nondominant SANE score was 85.2 (standard deviation 19.4). There was no difference in dominant arm SANE scores when stratified by arm injury history (4.6 [95% confidence interval: −14.9, 5.8]) or arm surgery history (−3.8 [95% confidence interval: 13.4, 5.8]). The shoulders had the greatest persistent joint pain prevalence (28% of all participants) and elbows (21% of all participants). There was no relationship between dominant arm pain or function and playing position. Conclusion This is the first study to demonstrate an increase in dominant arm disability in former baseball players. The high prevalence of persistent arm pain and poor arm function among former baseball players is concerning considering participants were younger than 40 years of age. No differences were observed in arm function when stratifying by arm history, surgery, or position demonstrating the potential relationship between baseball participation and arm disability after cessation of play. Clinicians should consider working with baseball players to develop long-term strategies to maintain joint health, especially in the throwing arm, when baseball players are transitioning to retirement. Future research is needed to understand the long-term effectiveness of clinical treatments and the implications of specific arm injuries such as ulnar collateral ligament tears on persistent arm pain and function.

BackgroundPhysical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants.MethodsTwenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone.ResultsParticipants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3).ConclusionsThere are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA.

Objective To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. Design We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle–Ottawa Scale (NOS) for risk of bias assessment. Results Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). Conclusions Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations., Osteoarthritis and Cartilage, 29 (5), ISSN:1063-4584, ISSN:1522-9653

To (1) evaluate an injury risk model that included modifiable and nonmodifiable factors into an arm injury risk prediction model in Minor League Baseball (MiLB) pitchers and (2) compare model performance separately for predicting the incidence of elbow and shoulder injuries.Prospective cohort.A 10-year MiLB injury risk study was conducted. Pitchers were evaluated during preseason, and pitches and arm injuries were documented prospectively. Nonmodifiable variables included arm injury history, professional experience, arm dominance, year, and humeral torsion. Modifiable variables included BMI, pitch count, total range of motion, and horizontal adduction. We compared modifiable, nonmodifiable, and combined model performance by R2, calibration (best = 1.00), and discrimination (area under the curve [AUC]; higher number is better). Sensitivity analysis included only arm injuries sustained in the first 90 days.In this study, 407 MiLB pitchers (141 arm injuries) were included. Arm injury incidence was 0.27 injuries per 1000 pitches. The arm injury model (calibration 1.05 [0.81-1.30]; AUC: 0.74 [0.69-0.80]) had improved performance compared to only using modifiable predictors (calibration: 0.91 [0.68-1.14]; AUC: 0.67 [0.62-0.73]) and only shoulder range of motion (calibration: 0.52 [0.29, 0.75]; AUC: 0.52 [0.46, 58]). Elbow injury model demonstrated improved performance (calibration: 1.03 [0.76-1.33]; AUC: 0.76 [0.69-0.83]) compared to the shoulder injury model (calibration: 0.46 [0.22-0.69]; AUC: 0.62 [95% CI: 0.55, 0.69]). The sensitivity analysis demonstrated improved model performance compared to the arm injury model.Arm injury risk is influenced by modifiable and nonmodifiable risk factors. The most accurate way to identify professional pitchers who are at risk for arm injury is to use a model that includes modifiable and nonmodifiable risk factors.

ObjectiveThe BRAIN Study was established to assess the associations between self-reported concussions and cognitive function among retired rugby players.MethodsFormer elite-level male rugby union players (50+ years) in England were recruited. Exposure to rugby-related concussion was collected using the BRAIN-Q tool. The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC). Linear regressions were conducted for the association between concussion and PACC score, adjusting for confounders.ResultsA total of 146 participants were recruited. The mean (standard deviation) length of playing career was 15.8 (5.4) years. A total of 79.5% reported rugby-related concussion(s). No association was found between concussion and PACC (β –0.03 [95% confidence interval (CI): –1.31, 0.26]). However, participants aged 80+ years reporting 3+ concussions had worse cognitive function than those without concussion (β –1.04 [95% CI: –1.62, –0.47]).ConclusionsOverall there was no association between concussion and cognitive function; however, a significant interaction with age revealed an association in older participants.

OBJECTIVE: To determine if playing position, a higher playing standard, and nonhelmet use are related to an increased odds of joint-specific injury and concussion in cricket. DESIGN: Cross-sectional cohort. PARTICIPANTS: Twenty-eight thousand one hundred fifty-two current or former recreational and high-performance cricketers registered on a national database were invited to participate in the Cricket Health and Wellbeing Study. Eligibility requirements were aged ≥18 years and played ≥1 cricket season. INDEPENDENT VARIABLES: Main playing position (bowler/batter/all-rounder), playing standard (high-performance/recreational), and helmet use (always/most of the time/occasionally/never). MAIN OUTCOME MEASURES: Cross-sectional questionnaire data included cricket-related injury (hip/groin, knee, ankle, shoulder, hand, back) resulting in ≥4 weeks of reduced exercise and self-reported concussion history. Crude and adjusted (adjusted for seasons played) odds ratios and 95% confidence interval (CIs) were estimated using logistic regression. RESULTS: Of 2294 participants (59% current cricketers; 97% male; age 52 ± 15 years; played 29 ± 15 seasons; 62% recreational cricketers), 47% reported cricket-related injury and 10% reported concussion. Bowlers had greater odds of hip/groin [odds ratio (95% CI), 1.9 (1.0-3.3)], knee [2.0 (1.4-2.8)], shoulder [2.9 (1.8-4.5)], and back [2.8 (1.7-4.4)] injury compared with batters. High-performance cricketers had greater odds of injury and concussion than recreational cricketers. Wearing a helmet most of the time [2.0 (1.4-3.0)] or occasionally [1.8 (1.3-2.6)] was related to higher odds of self-reported concussion compared with never wearing a helmet. Concussion rates were similar in cricketers who always and never wore a helmet. CONCLUSIONS: A higher playing standard and bowling (compared with batting) were associated with greater odds of injury. Wearing a helmet occasionally or most of the time was associated with higher odds of self-reported concussion compared with never wearing a helmet.

Objective Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. Methods We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren–Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. Results Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = −0.042, 95% CI −0.08, −0.0004). No other associations were observed. Conclusions In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

ObjectiveAs part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery.MethodsWe used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data.ResultsChronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain.ConclusionAlthough TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems.

Objectives:We aimed to investigate age- and sex-specific effects of obesity, metabolic syndrome (MetS) and its components on back pain in middle-aged and older English individuals. Methods:We used data from the English Longitudinal Study of Ageing, wave 2 (2004–2005).Body mass index(BMI) expressed the obesity, while MetS was defined according to revised Adult Treatment Panel (ATP) III criteria. We assessed associations between obesity, MetS and its components with presence and severity of back pain and provided estimates per strata, middle-aged (50–64years) and older (65–79years), women and men. Results:The study sample included 3328 participants, 1021 and 835 middle-aged women and men and 773 and 699 older women and men, respectively. We found that BMI (OR=1.07, 95% CI 1.05–1.09), MetS (OR=1.47, 95% CI 1.22–1.77), high waist circumference (WC), high triglycerides (TG), and high fasting blood glucose were associated with the presence of back pain. Effects of BMI were consistent across the strata. However, MetS was associated with back pain only in women, middle-aged (OR=1.59, 95% CI 1.14–2.21) and older (OR=1.43, 95% CI 1.01–2.05). The MetS component driving this association was high WC, supported by high TG in older women. Higher BMI, presence of MetS, high blood pressure and TG were associated with back pain severity. Conclusions:We found that obesity was associated with the presence and severity of back pain, irrespective of age and sex. However, we found women-specific effects of MetS driven by high WC, indicating that metabolic dysregulation contributes to back pain pathophysiology in women.

Progressive hand interphalangeal joint (IPJ) osteoarthritis is associated with pain, reduced function and impaired quality of life. However, the evidence surrounding risk factors for IPJ osteoarthritis progression is unclear. Identifying risk factors for IPJ osteoarthritis progression may inform preventative strategies and early interventions to improve long-term outcomes for individuals at risk of IPJ osteoarthritis progression. The objectives of the study were to describe methods used to measure the progression of IPJ osteoarthritis and identify risk factors for IPJ osteoarthritis progression. MEDLINE, EMBASE, Scopus, and The Cochrane Library were searched from inception to 19th February 2020 (PROSPERO CRD42019121034). Eligible studies assessed potential risk factor/s associated with IPJ osteoarthritis progression. Risk of bias was assessed using a modified QUIPS Tool, and a best evidence synthesis was performed. Of eight eligible studies, all measured osteoarthritis progression radiographically, and none considered symptoms. Eighteen potential risk factors were assessed. Diabetes (adjusted mean difference between 2.06 and 7.78), and larger finger epiphyseal index in males (regression coefficient β = 0.202) and females (β = 0.325) were identified as risk factors (limited evidence). Older age in men and women showed mixed results; 13 variables were not risk factors (all limited evidence). Patients with diabetes and larger finger epiphyseal index might be at higher risk of radiographic IPJ osteoarthritis progression, though evidence is limited and studies are biased. Studies assessing symptomatic IPJ osteoarthritis progression are lacking. Electronic supplementary material The online version of this article (10.1007/s00296-020-04687-1) contains supplementary material, which is available to authorized users.

Objective To assess the long-term prevalence, natural history, progression, and incidence of radiographic first metatarsophalangeal (MTP) joint osteoarthritis (OA). Methods A longitudinal cohort design was used in which radiographic OA at the first MTP joint was investigated in participants from the Chingford 1,000 Women Study at year 6 (1995) and year 23 (2013-2015). Radiographic features of osteophytes (OPs) and/or joint space narrowing (JSN) at the first MTP joint were scored according to a validated foot atlas. Natural history was determined by the change in prevalence, incidence, progression, and worsening of OA in the first MTP joint. Results Complete case-matched foot radiographic data were available for 193 of the women currently enrolled in the study (mean ± SD age 75.7 ± 5.2 years [range 69-90 years]). At the level of the first MTP joint, prevalence of OA at year 6 was 21.76% in the left and 24.35% in the right; at year 23, it was 23.83% in the left and 32.64% in the right. Over the 19-year period, 13.5% of the women developed incident OA in the right first MTP joint and 8.3% in the left. Both progression and worsening of OA were more evident for OPs and in the right first MTP joints. Conclusion In this study of the natural history of radiographic first MTP joint OA, which to our knowledge is the longest study to date, the prevalence and incidence of first MTP joint OA increased over a 19-year period. Progression and/or worsening of OA at the first MTP joint over time appears to be driven by OP development rather than JSN, which suggests a biomechanical cause.

ObjectivesTo investigate the rates of return to work and workability among working-age people following total hip arthroplasty (THA).MethodsParticipants from the Geneva Arthroplasty Registry and the Clinical Outcomes for Arthroplasty Study aged 18–64 years when they had primary THA and with at least 5 years’ follow-up were mailed a questionnaire 2017–2019. Information was collected about preoperative and post-THA employment along with exposure to physically demanding activities at work or in leisure. Patterns of change of job were explored. Survival analyses using Cox proportional hazard models were created to explore risk factors for having to stop work because of difficulties with the replaced hip.ResultsIn total, 825 returned a questionnaire (response 58%), 392 (48%) men, mean age 58 years, median follow-up 7.5 years post-THA. The majority (93%) of those who worked preoperatively returned to work, mostly in the same sector but higher rates of non-return (36%–41%) were seen among process, plant and machine operatives and workers in elementary occupations. 7% reported subsequently leaving work because of their replaced hip and the risk of this was strongly associated with: standing >4 hours/day (HR 3.81, 95% CI 1.62 to 8.96); kneeling/squatting (HR 3.32, 95% CI 1.46 to 7.55) and/or carrying/lifting ≥10 kg (HR 5.43, 95% CI 2.29 to 12.88).ConclusionsIt may be more difficult to return to some (particularly physically demanding) jobs post-THA than others. Rehabilitation may need to be targeted to these types of workers or it may be that redeployment or job change counselling are required.

Background We aimed to quantify the association between chronic musculoskeletal pain and all-cause mortality, and to investigate the extent to which this association is mediated by physical activity, smoking status, alcohol consumption, and opioid use. Methods For this population-based cohort study, we used data from UK Biobank, UK between baseline visit (2006–2010) to 18th December 2020. We assessed the associations between chronic musculoskeletal pain and all-cause mortality using a Cox proportional hazards model. We performed causal mediation analyses to examine the proportion of the association between chronic musculoskeletal pain and all-cause mortality. Findings Of the 384,367 included participants, a total of 187,269 participants reported chronic musculoskeletal pain. Higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain (e.g., four sites vs no site of pain, Hazard Ratio [HR] 1.46, 95% Confidence Interval [CI] 1.35 to 1.57). The multiple mediator analyses showed that the mediating proportions of all four mediators ranged from 53.4% to 122.6%: among participants with two or more pain sites, the effect estimate reduced substantially, for example, HR reduced from 1.25 (95% CI: 1.21 to 1.30; two pain sites) to 1.07 (95% CI: 1.01 to 1.11; two pain sites). Interpretation We found that higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain, and at least half of the association of chronic musculoskeletal pain with increased all-cause mortality may be accounted for by four mediators. Funding Twins Research Australia.

In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.

Objective: Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting. Material and methods: A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a preexisting diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA. Results: 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2,768 (2.6%) were diagnosed with RA within 1 year as were 1,141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4 to 72.2), specificity 78.7% (78.6 to 78.8), and positive and negative predictive values 2.6% (2.5 to 2.7) and 99.7% (99.6 to 99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1,432 per true positive case. Conclusions: Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing.

Objectives To examine whether foot and/or ankle pain increases the risk of knee OA. Design We utilised longitudinal data from the Multicentre Osteoarthritis Study (MOST); a community-based cohort of risk factors for knee OA. Participants without frequent knee pain (clinic visit only) and radiographic knee OA (RKOA) at baseline and, with no evidence of musculoskeletal disease and a history of knee-related surgery were followed for up to 84-months for incident outcomes; i) RKOA (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent pain in the same knee) and iii) frequent knee pain only. At baseline, ankle and foot symptoms were assessed, with knee radiographs and symptoms also assessed at 30, 60 and 84-months. Our exposures included baseline ankle, foot, and ankle and foot pain (participant-level). Associations between foot and/or ankle pain and incident outcomes were assessed using multiple logistic regression, with adjustment for participant characteristics and ankle/foot pain. Results No statistically significant associations were observed between ankle, foot and, ankle and foot pain and incident RKOA, respectively. Ankle pain with (2.30, 95% CI 1.13 to 4.66) and without foot pain (OR: 2.53, 95% CI 1.34 to 4.80) were associated with increased odds of incident symptomatic RKOA and frequent knee pain. No statistically significant associations were observed between foot pain and these outcomes. Conclusions Ankle pain should be a focus point, more so than foot pain, in the management of knee OA. Future studies should include additional ankle joint-specific symptom questions to better elucidate the knee OA biomechanical pathway.

Background: A comprehensive understanding of lifestyle (health conditions and substance use), health-related quality of life (HRQoL), flourishing (holistic representation of health), and physical activity can inform stakeholders (players, coaches, and clinicians) and help improve long-term health across the life span. Purpose: To describe health conditions (comorbidities or diagnoses), substance use, physical activity, HRQoL, and flourishing in current and former collegiate and professional baseball players and to assess the relationship between playing position and HRQoL/flourishing in former baseball players. Study Design: Descriptive epidemiology study. Methods: Eligible participants were those ≥18 years old with ≥1 season of collegiate or professional baseball experience. Participants completed a survey on health conditions (asthma, diabetes, hypertension, hypercholesterolemia, and depression), substance use (tobacco, alcohol, and energy drinks), physical activity (International Physical Activity Questionnaire–Short Form), HRQoL (Veterans Rand 12-Item Health Survey [VR-12] physical and mental component scores), and flourishing (Flourishing Scale). Adjusted multivariable regressions were performed for HRQoL and flourishing. Results: Overall, 260 baseball players opened the survey, and 214 (current players, 97; former players, 117) participated for an 82% response rate. Of the former players, 32% had hypertension or hypercholesterolemia. In addition, 26% of current players had used smokeless tobacco (median, 3 years; interquartile range [IQR], 1-5 years) as compared with 34% of former players (median, 15 years; IQR, 5-25 years). In addition, 14% of current players had used electronic cigarettes (median, 2 years; IQR, 0-4 years) as opposed to 3% of former (median, 3 years; IQR, 2-4 years). Energy drinks were consumed by 31% and 14%, respectively, of current and former players on at least a weekly basis. Current baseball players performed 8667 metabolic equivalents per week of physical activity as opposed to 3931 in former players. Pitching was associated with worse VR-12 Mental Component Scores (–5.0; 95% confidence interval, –9.0 to –1.0). Playing position was not related to VR-12 Physical Component Scores or flourishing in former baseball players. Conclusion: The similar smokeless tobacco prevalence between current and former baseball players suggests that they may start using tobacco products during baseball participation and continue after retirement. Similar reported HRQoL as compared with the general US population and high flourishing and physical activity levels suggest that baseball players may present with good musculoskeletal and psychological health.

Background Although routine NHS data potentially include all patients, confounding limits their use for causal inference. Methods to minimise confounding in observational studies of implantable devices are required to enable the evaluation of patients with severe systemic morbidity who are excluded from many randomised controlled trials. Objectives Stage 1 – replicate the Total or Partial Knee Arthroplasty Trial (TOPKAT), a surgical randomised controlled trial comparing unicompartmental knee replacement with total knee replacement using propensity score and instrumental variable methods. Stage 2 – compare the risk benefits and cost-effectiveness of unicompartmental knee replacement with total knee replacement surgery in patients with severe systemic morbidity who would have been ineligible for TOPKAT using the validated methods from stage 1. Design This was a cohort study. Setting Data were obtained from the National Joint Registry database and linked to hospital inpatient (Hospital Episode Statistics) and patient-reported outcome data. Participants Stage 1 – people undergoing unicompartmental knee replacement surgery or total knee replacement surgery who met the TOPKAT eligibility criteria. Stage 2 – participants with an American Society of Anesthesiologists grade of ≥ 3. Intervention The patients were exposed to either unicompartmental knee replacement surgery or total knee replacement surgery. Main outcome measures The primary outcome measure was the postoperative Oxford Knee Score. The secondary outcome measures were 90-day postoperative complications (venous thromboembolism, myocardial infarction and prosthetic joint infection) and 5-year revision risk and mortality. The main outcome measures for the health economic analysis were health-related quality of life (EuroQol-5 Dimensions) and NHS hospital costs. Results In stage 1, propensity score stratification and inverse probability weighting replicated the results of TOPKAT. Propensity score adjustment, propensity score matching and instrumental variables did not. Stage 2 included 2256 unicompartmental knee replacement patients and 57,682 total knee replacement patients who had severe comorbidities, of whom 145 and 23,344 had linked Oxford Knee Scores, respectively. A statistically significant but clinically irrelevant difference favouring unicompartmental knee replacement was observed, with a mean postoperative Oxford Knee Score difference of Limitations Although some propensity score methods successfully replicated TOPKAT, unresolved confounding may have affected stage 2. Missing Oxford Knee Scores may have led to information bias. Conclusions Propensity score stratification and inverse probability weighting successfully replicated TOPKAT, implying that some (but not all) propensity score methods can be used to evaluate surgical innovations and implantable medical devices using routine NHS data. Unicompartmental knee replacement was safer and more cost-effective than total knee replacement for patients with severe comorbidity and should be considered the first option for suitable patients. Future work Further research is required to understand the performance of propensity score methods for evaluating surgical innovations and implantable devices. Trial registration This trial is registered as EUPAS17435. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 66. See the NIHR Journals Library website for further project information.

Objective Our aims were to examine the effects of heeled shoes on incident knee osteoarthritis (OA) and joint pain. Methods We used longitudinal data from the Chingford 1000 Women Study (Chingford Study), a prospective cohort of women aged 50 years or older. Participants with musculoskeletal disorders and/or a history of knee-related injury/surgery were excluded. Participants were followed for up to 5 years for incident outcomes including 1) radiographic knee OA (RKOA) and 2) joint pain (feet, knees, hips, and back). Footwear data, including ever worn heels of 2 inches or more and daytime/evening hours (per week) spent wearing heeled shoes over five decades (ages 50 years), were available at Year 10 whereas knee radiographs and joint symptom data were also collected at Year 15. Cumulative time spent wearing heeled shoes was calculated for women reporting ever-use of heeled shoes (≥2 inches). Multiple logistic regression was used to examine the relationship between exposures and outcomes (from Year 10 to Year 15). Results A total of 356 women were eligible at Year 10 with a median (interquartile range) age of 60 (56-65) years. Compared with non-use, ever-use of heeled shoes (≥2 inches) was not associated with incident RKOA (1.35; 95% confidence interval: 0.56-3.27). No associations were observed between increasing cumulative time spent wearing heels and incident outcomes. Conclusion Compared with the non-use of heeled shoes, ever-use of heels (≥2 inches) was not associated with incident RKOA and incident joint symptoms. Further, increasing cumulative time spent wearing heels was not associated with any of our outcomes.

Objective The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. Methods Data were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5–12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. Results Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93–1.12]), radiographic OA (RR 1.00 [95% CI 0.94–1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96–1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. Conclusions Our findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.

Background Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury. Methods This longitudinal cohort study recruited individuals aged 16–50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS4. This study is registered with ClinicalTrials.gov, number NCT02667756. Findings We enrolled 150 patients at a median of 17 days (range 1–59, IQR 9–26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16–50, IQR 21–30). 98 (65%) of 150 participants completed a KOOS4 at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS4 (n=77; coefficient −20·5, 95% CI −34·8 to −6·18; p=0·0060). The only predefined biomarkers that showed independent associations with 2-year KOOS4 were synovial fluid MCP-1 (n=77; −0·015, 0·027 to −0·004 per change in 1 pg/mL units; p=0·011) and IL-6 (n=77; −0·0005, −0·0009 to −0·0001 per change in 1 pg/mL units; p=0·017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture). Interpretation The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic outcomes but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process need to be better understood to make clinical progress. Funding Versus Arthritis, Kennedy Trust for Rheumatology Research, and NIHR Oxford Biomedical Research Centre.

Background: while reports indicate the association between obesity and back pain, its mechanism is still unclear. Thus, we aimed to investigate the effects of weight and its components on back pain in middle-aged women while considering direct mechanical and indirect effects via inflammatory and metabolic parameters.Methods: we used data from the Chingford 1000 Women Study, two follow-ups seven years apart. We assessed effects of weight, body mass index (BMI), total fat mass (TFM), total lean mass (TLM) and total bone mineral density (TBMD), measured by dual-energy X-ray absorptiometry, on back pain episode. We used inflammatory (C-reactive protein, interleukin-6, and tumour necrosis factor-alpha) and metabolic parameters (systolic and diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and fasting blood glucose) as mediators of indirect effects. We investigated associations of interest cross-sectionally and longitudinally using binary logistic regression and parallel mediation model.Results: we included 826 Chingford middle-aged women (mean age=60.7, SD=5.9) from the first used follow-up in cross-sectional and mediation analyses and 645 women that attended the follow-up seven years later, in longitudinal analyses. We found that increased weight was directly associated with increased odds of having back pain episode (OR=1.02; 95% CI 1.01-1.03), similarly as BMI (OR=1.05; 95% CI 1.02-1.08) and TFM (OR=1.03; 95% CI 1.01-1.04) consistently across the cross-sectional and longitudinal models, but not TLM or TBMD. However, we did not find consistent indirect effects of weight or its components through measured inflammatory or metabolic parameters on back pain.Conclusions: our results show that in middle-aged women, weight, BMI and TFM are directly related to back pain, indicating prominence of mechanical loading effect.

In osteoarthritis (OA) clinical trials, reliable and responsive outcome measures to document physical and functional improvements are limited.This study aimed to assess whether the use of an activity tracker in an OA clinical trial is a responsive measurement tool. Secondary objectives assessed feasibility and validity.We recruited 65 participants in a prospective cohort study nested in a placebo-controlled clinical trial of platelet-rich plasma injection in knee OA. Participants wore an activity tracker (Fitbit Flex 2), and a smartphone was preloaded with a mobile application (OApp) designed to monitor load rates as a surrogate of knee loading. Participants used the systems for 7 days at baseline and for 7 days before the 2-month follow-up assessment. Effect size (ES) and standardised response mean (SRM) were calculated for change in step count and knee loading rate and regularly used knee OA outcome measures. Correlation coefficients (r) were calculated to examine the strength of the association between outcome measures.. Step count showed a trivial ES and SRM and mean knee loading rate measurements a moderate ES and SRM. We found a weak but significant correlation between change in mean steps per day and global improvement overall (r= 0.28) and Western Ontario and McMaster Universities Osteoarthritis Index function (r = -0.28). Compliance was high with the activity trackers.Despite good feasibility, this study did not show significant responsiveness or validity of the activity trackers as compared with currently recommended outcome measures in OA clinical trials. The main challenge is the lack of a gold standard outcome measure to validate against, and because of the complex interplay between pain and measured function, a lack of correlation does not necessarily represent a failed validation in this context.ACTRN12617000853347. This trial is a substudy of the "Platelet-rich plasma as a symptom-and disease-modifying treatment for knee osteoarthritis - the RESTORE trial".

Objective We aimed to study 19-year body mass index (BMI) patterns and their (1) bidirectional relationship with musculoskeletal pain and (2) mortality risk. Study design and Setting We used data from the Chingford study and group-based trajectory modelling to define 19-year BMI patterns. We investigated whether baseline back, hand, hip, and knee pain (as single- and multi-site) predicted 19-year BMI trajectory, and whether 19-year BMI patterns predicted pain in year 20. We explored BMI trajectories and mortality risk over 25 years (life expectancy). Results We included 938 women (mean age: year-1=54, year-20=72) and found seven distinct 19-year BMI trajectories: two normal-weighted (reference), slightly overweight, lower and upper overweight-to-obese, lower and upper obese. BMI patterns capturing the increase overweight-to-obese (BMI 27-34 overtime) were bidirectionally related to knee and multi-site pain. The lower obese pattern (BMI 33-38) was unidirectionally associated with lower limb pain. Women with BMI above 40 had an increased all-cause and cardiovascular mortality risk. Conclusions For most postmenopausal women, the overweight WHO category was a transition. Two patterns capturing increase overweight-to-obese were mutually related to musculoskeletal pain, i.e., knee and multi-site pain contributed to becoming obese, and trajectories of becoming obese increased the odds of experiencing pain later.

To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.