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Background The objective was to summarize the methodology used to reach consensus for recommended minimum data elements that should be collected and reported when conducting injury surveillance research in military settings. This paper summarizes the methodology used to develop the international Minimum Data Elements for surveillance and Reporting of Musculoskeletal Injuries in the MILitary (ROMMIL) statement. Methods A Delphi methodology was employed to reach consensus for minimum reporting elements. Preliminary steps included conducting a literature review and surveying a convenience sample of military stakeholders to 1) identify barriers and facilitators of military musculoskeletal injury (MSKI) prevention programs, 2) identify relevant knowledge/information gaps and 3) establish future research priorities. The team then led a sequential three-round Delphi consensus survey, including relevant stakeholders from militaries around the world, and then conducted asynchronous mixed knowledge user meeting to explore level of agreement among subject matter experts. Knowledge users, including former and current military service members, civil servant practitioners, and global-wide subject matter experts having experience with policy, execution, or clinical investigation of MSKI mitigation programs, MSKI diagnoses, and MSKI risk factors in military settings. For each round, participants scored each question on a Likert scale of 1-5. Scores ranged from No Importance (1) to Strong Importance (5). Results Literature review and surveys helped informed the scope of potential variables to vote on. Three rounds were necessary to reach minimum consensus. Ninety-five, 65 and 42 respondents participated in the first, second and third rounds of the Delphi consensus, respectively. Ultimately, consensus recommendations emerged consisting of one data principle and 33 minimum data elements. Conclusions Achieving consensus across relevant stakeholders representing military organizations globally can be challenging. This paper details the methodology employed to reach consensus for a core minimum data elements checklist for conducting MSKI research in military settings and improve data harmonization and scalability efforts. These methods can be used as a resource to assist in future consensus endeavors of similar nature.

Background The objective was to summarize the methodology used to reach consensus for recommended minimum data elements that should be collected and reported when conducting injury surveillance research in military settings. This paper summarizes the methodology used to develop the international Minimum Data Elements for surveillance and Reporting of Musculoskeletal Injuries in the MILitary (ROMMIL) statement. Methods A Delphi methodology was employed to reach consensus for minimum reporting elements. Preliminary steps included conducting a literature review and surveying a convenience sample of military stakeholders to 1) identify barriers and facilitators of military musculoskeletal injury (MSKI) prevention programs, 2) identify relevant knowledge/information gaps and 3) establish future research priorities. The team then led a sequential three-round Delphi consensus survey, including relevant stakeholders from militaries around the world, and then conducted asynchronous mixed knowledge user meeting to explore level of agreement among subject matter experts. Knowledge users, including former and current military service members, civil servant practitioners, and global-wide subject matter experts having experience with policy, execution, or clinical investigation of MSKI mitigation programs, MSKI diagnoses, and MSKI risk factors in military settings. For each round, participants scored each question on a Likert scale of 1-5. Scores ranged from No Importance (1) to Strong Importance (5). Results Literature review and surveys helped informed the scope of potential variables to vote on. Three rounds were necessary to reach minimum consensus. Ninety-five, 65 and 42 respondents participated in the first, second and third rounds of the Delphi consensus, respectively. Ultimately, consensus recommendations emerged consisting of one data principle and 33 minimum data elements. Conclusions Achieving consensus across relevant stakeholders representing military organizations globally can be challenging. This paper details the methodology employed to reach consensus for a core minimum data elements checklist for conducting MSKI research in military settings and improve data harmonization and scalability efforts. These methods can be used as a resource to assist in future consensus endeavors of similar nature.

Objective To estimate the age-specific lifetime prevalence of skin cancer in a sample of Australian golf participants and estimate skin cancer risk in golf participants compared with a general population-based sample.Methods Golf participants in Australia (n=336) completed the Australian Golf Health Survey which collected data on skin cancer diagnosis (self-reported history), physical activity levels and participant demographics. Data were compared with a sample of the Australian general population (n=15780, Australian Health Survey). Age-specific lifetime prevalence of skin cancer in golf and general population-based samples was determined, and modified Poisson regression (adjusted for age, sex, education and smoking status) was used to estimate the association between playing golf and the risk of a current or past skin cancer diagnosis.Results One in four golf participants (n=91; 27%) had received a skin cancer diagnosis compared with 7% (n=1173) of the general population. Golf participants were 2.42 (2.01 to 2.91) (relative risk (95% CI)) times more likely to report a skin cancer diagnosis than the general population after adjusting for age, sex, education and smoking status.Conclusion Playing golf in Australia is associated with a higher age-specific lifetime prevalence of skin cancer compared with the general population. Golf organisations, clubs and facilities should inform golf participants about the risk of skin cancer and promote preventive strategies including use of high-Sun Protection Factor (SPF) sunscreen, appropriate hats and clothing.

# Background Baseball injuries are a significant problem and have increased in incidence over the last decade. Reporting injury incidence only gives context to rate but not in relation to severity or injury time loss. # Hypothesis/Purpose The purpose of this study was to 1) incorporate both modifiable and non-modifiable factors to develop an arm injury burden prediction model in Minor League Baseball (MiLB) pitchers; and 2) understand how the model performs separately on elbow and shoulder injury burden. # Study Design Prospective longitudinal study # Methods The study was conducted from 2013 to 2019 on MiLB pitchers. Pitchers were evaluated in spring training arm for shoulder range of motion and injuries were followed throughout the season. A model to predict arm injury burden was produced using zero inflated negative binomial regression. Internal validation was performed using ten-fold cross validation. Subgroup analyses were performed for elbow and shoulder separately. Model performance was assessed with root mean square error (RMSE), model fit (R2), and calibration with 95% confidence intervals (95% CI). # Results Two-hundred, ninety-seven pitchers (94 injuries) were included with an injury incidence of 1.15 arm injuries per 1000 athletic exposures. Median days lost to an arm injury was 58 (11, 106). The final model demonstrated good prediction ability (RMSE: 11.9 days, R^2^: 0.80) and a calibration slope of 0.98 (95% CI: 0.92, 1.04). A separate elbow model demonstrated weaker predictive performance (RMSE: 21.3; R^2^: 0.42; calibration: 1.25 \[1.16, 1.34]), as did a separate shoulder model (RMSE: 17.9; R^2^: 0.57; calibration: 1.01 \[0.92, 1.10\]). # Conclusions The injury burden prediction model demonstrated excellent performance. Caution should be advised with predictions between one to 14 days lost to arm injury. Separate elbow and shoulder prediction models demonstrated decreased performance. The inclusion of both modifiable and non-modifiable factors into a comprehensive injury burden model provides the most accurate prediction of days lost in professional pitchers. # Level of Evidence 2

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.

Abstract Background Ankle arthroplasty, commonly known as ankle replacement, is a surgical procedure for treating end‐stage ankle osteoarthritis. Whilst evidence shows good clinical results after surgery, little is known of the long‐term survival of ankle replacements and the need for ankle revision. Using more recent implant data and long‐term data, there is now opportunity to examine at a population‐level the survival rate for ankle implants, to examine between‐country differences in ankle revision surgery, and to compare temporal trends in revision rates between countries. Methods Four national joint registries from Australia, New Zealand, Norway and Sweden provided the necessary data on revision outcome following primary ankle replacement, for various periods of observation – the earliest starting in 1993 up to the end of 2019. Data were either acquired from published, online annual reports or were provided from direct contact with the joint registries. The key information extracted were Kaplan‐Meier estimates to plot survival probability curves following primary ankle replacement. Results The survival rates varied between countries. At 2 years, across all registries, survival rates all exceeded 0.9 (range 0.91 to 0.97). The variation widened at 5 years (range 0.80 to 0.91), at 10 years (range 0.66 to 0.84) and further at 15‐years follow‐up (0.56 to 0.78). At each time point, implant survival was greater in Australia and New Zealand with lower rates in Sweden and Norway. Conclusions We observed variation in primary ankle replacement survival rates across these national registries, although even after 5 years, these population derived data show an 80% revision free survival. These data raise a number of hypotheses concerning the reasons for between‐country differences in revision‐free survival which will require access to primary data for analysis.

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 inflammatory 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: 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

OBJECTIVES The BRAIN-Q is a tool aimed at maximising the accuracy and minimising measurement error for retrospectively assessing concussions. This paper reports the agreement of the BRAIN-Q tool when compared to extant questionnaire questions, and its reproducibility when compared with its telephonic version (tBRAIN-Q). METHODS The BRAIN-Q entails a 3-stage process: defining a concussion, creating a visual timeline with life events, and establishing detailed characteristics for each reported concussion. It was designed to be administered in-person by trained personnel, and was used in the BRAIN study. Its performance was compared with the MSK study, which previously collected a few questions in a broader self-administered questionnaire, and with the tBRAIN-Q Recall, its telephonic version. RESULTS In total, 101 participants were included, of whom 9 were re-assessed with the tBRAIN-Q. The agreement of the BRAIN-Q with the muscle skeletal-questionnaire for rugby-related concussion was 86.7% (κ=0.6). Rugby-related concussion with loss of consciousness showed lower agreement (82.0%; κ=0.6). The comparison between the BRAIN-Q and the tBRAIN-Q showed good reproducibility. CONCLUSIONS The BRAIN-Q is a relatively easy tool to administer in face-to-face assessments, and it showed optimal reproducibility. It includes a well-established definition of concussion, and is used to collect detailed information on each concussion, allowing for a number of subgroup analyses (e.g., by severity, age, or context). The BRAIN-Q is easily adaptable to other sporting settings.

Objective: To identify post-operative risk factors for the development of chronic pain after knee replacement. Design: Primary knee replacements in persons aged ≥18 years between April 2008 and December 2016 from the National Joint Registry, linked with English Hospital Episode Statistics data, and Patient Reported Outcome Measures. The outcome was chronic pain 6-months after surgery (Oxford Knee pain score). Logistic regression modelling identified risk factors for chronic pain outcome. Results: 258,386 patients; 56.7% women; average age 70.1 years (SD ​± ​8.8 years). 43,702 (16.9%) were identified as having chronic pain 6-months post-surgery. Within 3 months of surgery complications were uncommon: intra-operative complications 1224 (0.5%); ≥1 medical complication 6073 (2.4%)); 32,930 (12.7%) hospital readmissions; 3848 (1.5%) re-operation; 835 (0.3%) revision. Post-surgical risk factors of chronic pain were: mechanical complication of prosthesis odds ratio (OR) 1.56 (95% Confidence Interval 1.35, 1.80); surgical site infection OR 1.13 (0.99, 1.29); readmission OR 1.47 (1.42, 1.52); re-operation OR 1.39 (1.27, 1.51); revision OR 1.92 (1.64, 2.25); length of stay e.g. 6+ vs.

Objective Identify risk factors for poor pain outcomes six months after primary knee replacement surgery. Methods Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale. Results are presented as relative risk ratios and adjusted risk differences (ARD) by fitting a generalized linear model with a binomial error structure and log link function. Results Information was available for 4,750 patients from 2009 to 2016, with a mean age of 69, of whom 56.1% were female. 10.4% of patients had poor pain outcomes. The strongest effects were seen for pre-operative factors: mild knee pain symptoms at the time of surgery (ARD 18.2% (95% Confidence Interval 13.6, 22.8), smoking 12.0% (95% CI:7.3, 16.6), living in the most deprived areas 5.6% (95% CI:2.3, 9.0) and obesity class II 6.3% (95% CI:3.0, 9.7). Important risk factors with more moderate effects included a history of previous knee arthroscopy surgery 4.6% (95% CI:2.5, 6.6), and use of opioids 3.4% (95% CI:1.4, 5.3) within three months after surgery. Those patients with worsening pain state change had more complications by 3 months (11.8% among those in a worse pain state vs. 2.7% with the same pain state). Conclusions We quantified the relative importance of individual risk factors including mild pre-operative pain, smoking, deprivation, obesity and opioid use in terms of the absolute proportions of patients achieving poor pain outcomes. These findings will support development of interventions to reduce the numbers of patients who have poor pain outcomes.

Objectives To estimate the relationship between patient characteristics and referral decisions made by musculoskeletal hubs, and to assess the possible impact of an evidence-based referral tool.Design Retrospective analysis of medical records and decision tree model evaluating policy changes using local and national data.Setting One musculoskeletal interface clinic (hub) in England.Participants 922 adults aged ≥50 years referred by general practitioners with symptoms of knee or hip osteoarthritis.Interventions We assessed the current frequency and determinants of referrals from one hub and the change in referrals that would occur at this centre and nationally if evidence-based thresholds for referral (Oxford Knee and Hip Scores, OKS/OHS) were introduced.Main outcome measure OKS/OHS, referrals for surgical assessment, referrals for arthroplasty, costs and quality-adjusted life years.Results Of 110 patients with knee symptoms attending face-to-face hub consultations, 49 (45%) were referred for surgical assessment; the mean OKS for these 49 patients was 18 (range: 1–41). Of 101 hip patients, 36 (36%) were referred for surgical assessment (mean OHS: 21, range: 5–44). No patients referred for surgical assessment were above previously reported economic thresholds for OKS (43) or OHS (45). Setting thresholds of OKS ≤31 and OHS ≤35 might have resulted in an additional 22 knee referrals and 26 hip referrals in our cohort. Extrapolating hub results across England suggests a possible increase in referrals nationally, of around 13 000 additional knee replacements and 4500 additional hip replacements each year.Conclusions Musculoskeletal hubs currently consider OKS/OHS and other factors when making decisions about referral to secondary care for joint replacement. Those referred typically have low OHS/OKS, and introducing evidence-based OKS/OHS thresholds would prevent few inappropriate (high-functioning, low-pain) referrals. However, our findings suggest that some patients not currently referred could benefit from arthroplasty based on OKS/OHS. More research is required to explore other important patient characteristics currently influencing hub decisions.

Background: Late-stage medial compartment knee osteoarthritis can be treated using total knee replacement or partial (unicompartmental) knee replacement. There is high variation in treatment choice and insufficient evidence to guide selection. Objective: To assess the clinical effectiveness and cost-effectiveness of partial knee replacement compared with total knee replacement in patients with medial compartment knee osteoarthritis. The findings are intended to guide surgical decision-making for patients, surgeons and health-care providers. Design: This was a randomised, multicentre, pragmatic comparative effectiveness trial that included an expertise component. The target sample size was 500 patients. A web-based randomisation system was used to allocate treatments. Setting: Twenty-seven NHS hospitals (68 surgeons). Participants: Patients with medial compartment knee osteoarthritis. Interventions: The trial compared the overall management strategy of partial knee replacement treatment with total knee replacement treatment. No specified brand or subtype of implant was investigated. Main outcome measures: The Oxford Knee Score at 5 years was the primary end point. Secondary outcomes included activity scores, global health measures, transition items, patient satisfaction (Lund Score) and complications (including reoperation, revision and composite ‘failure’ – defined by minimal Oxford Knee Score improvement and/or reoperation). Cost-effectiveness was also assessed. Results: A total of 528 patients were randomised (partial knee replacement, n = 264; total knee replacement, n = 264). The follow-up primary outcome response rate at 5 years was 88% and both operations had good outcomes. There was no significant difference between groups in mean Oxford Knee Score at 5 years (difference 1.04, 95% confidence interval –0.42 to 2.50). An area under the curve analysis of the Oxford Knee Score at 5 years showed benefit in favour of partial knee replacement over total knee replacement, but the difference was within the minimal clinically important difference [mean 36.6 (standard deviation 8.3) (n = 233), mean 35.1 (standard deviation 9.1) (n = 231), respectively]. Secondary outcome measures showed consistent patterns of benefit in the direction of partial knee replacement compared with total knee replacement although most differences were small and non-significant. Patient-reported improvement (transition) and reflection (would you have the operation again?) showed statistically significant superiority for partial knee replacement only, but both of these variables could be influenced by the lack of blinding. The frequency of reoperation (including revision) by treatment received was similar for both groups: 22 out of 245 for partial knee replacement and 28 out of 269 for total knee replacement patients. Revision rates at 5 years were 10 out of 245 for partial knee replacement and 8 out of 269 for total knee replacement. There were 28 ‘failures’ of partial knee replacement and 38 ‘failures’ of total knee replacement (as defined by composite outcome). Beyond 1 year, partial knee replacement was cost-effective compared with total knee replacement, being associated with greater health benefits (measured using quality-adjusted life-years) and lower health-care costs, reflecting lower costs of the index surgery and subsequent health-care use. Limitations: It was not possible to blind patients in this study and there was some non-compliance with the allocated treatment interventions. Surgeons providing partial knee replacement were relatively experienced with the procedure. Conclusions: Both total knee replacement and partial knee replacement are effective, offer similar clinical outcomes and have similar reoperation and complication rates. Some patient-reported measures of treatment approval were significantly higher for partial knee replacement than for total knee replacement. Partial knee replacement was more cost-effective (more effective and cost saving) than total knee replacement at 5 years. Future work: Further (10-year) follow-up is in progress to assess the longer-term stability of these findings. Trial registration: Current Controlled Trials ISRCTN03013488 and ClinicalTrials.gov NCT01352247. 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. 24, No. 20. See the NIHR Journals Library website for further project information.

Background: There is limited evidence concerning the effectiveness of enhanced recovery programmes in hip and knee replacement surgery, particularly when applied nationwide across a health-care system. Objectives: To determine the effect of hospital organisation, surgical factors and the enhanced recovery after surgery pathway on patient outcomes and NHS costs of hip and knee replacement. Design: (1) Statistical analysis of national linked data to explore geographical variations in patient outcomes of surgery. (2) A natural experimental study to determine clinical effectiveness of enhanced recovery after surgery. (3) A qualitative study to identify barriers to, and facilitators of, change. (4) Health economics analysis to establish NHS costs and cost-effectiveness. Setting: Data from the National Joint Registry, linked to English Hospital Episode Statistics and patient-reported outcome measures in both the geographical variation and natural experiment studies, together with the economic evaluation. The ethnographic study took place in four hospitals in a region of England. Participants: Qualitative study – 38 health professionals working in hip and knee replacement services in secondary care and 37 patients receiving hip or knee replacement. Interventions: Natural experiment – implementation of enhanced recovery after surgery at each hospital between 2009 and 2011. Enhanced recovery after surgery is a complex intervention focusing on several areas of patients’ care pathways through surgery: preoperatively (patient is in best possible condition for surgery), perioperatively (patient has best possible management during and after operation) and postoperatively (patient experiences best rehabilitation). Main outcome measures: Patient-reported pain and function (Oxford Hip Score/Oxford Knee Score); 6-month complications; length of stay; bed-day costs; and revision surgery within 5 years. Results: Geographical study – there are potentially unwarranted variations in patient outcomes of hip and knee replacement surgery. This variation cannot be explained by differences in patients, case mix, surgical or hospital organisational factors. Qualitative – successful implementation depends on empowering patients to work towards their recovery, providing post-discharge support and promoting successful multidisciplinary team working. Care processes were negotiated between patients and health-care professionals. ‘Good care’ remains an aspiration, particularly in the post-discharge period. Natural experiment – length of stay has declined substantially, pain and function have improved, revision rates are in decline and complication rates remain stable. The introduction of a national enhanced recovery after surgery programme maintained improvement, but did not alter the rate of change already under way. Health economics – costs are high in the year of joint replacement and remain higher in the subsequent year after surgery. There is a strong economic incentive to identify ways of reducing revisions and complications following joint replacement. Published cost-effectiveness evidence supports enhanced recovery pathways as a whole. Limitations: Short duration of follow-up data prior to enhanced recovery after surgery implementation and missing data, particularly for hospital organisation factors. Conclusion: No evidence was found to show that enhanced recovery after surgery had a substantial impact on longer-term downwards trends in costs and length of stay. Trends of improving outcomes were seen across all age groups, in those with and without comorbidity, and had begun prior to the formal enhanced recovery after surgery roll-out. Reductions in length of stay have been achieved without adversely affecting patient outcomes, yet, substantial variation remains in outcomes between hospital trusts. Future work: There is still work to be done to reduce and understand unwarranted variations in outcome between individual hospitals. Study registration: This study is registered as PROSPERO CRD42017059473. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 4. See the NIHR Journals Library website for further project information.

Abstract Background The prevalence of foot osteoarthritis (OA) is much less understood than hip, knee and hand OA. The foot is anatomically complex and different researchers have investigated different joints with lack of methodological standardisation across studies. The La Trobe Foot Atlas (LFA) is the first to address these issues in providing quantitative assessment of radiographic foot OA, but has not been tested externally. The aim of this study was to evaluate three different interpretive approaches to using the LFA for grading OA when scoring is difficult due to indistinct views of interosseous space and joint contour. Methods Foot radiographs of all remaining participants (n = 218) assessed in the Chingford Women Study 23 year visit (mean (SD) for age: 75.5 years (5.1)) were scored using the LFA defined protocol (Technique 1). Two revised scoring strategies were applied to the radiographs in addition to the standard LFA analyses. Technique 2 categorised joints that were difficult to grade as ‘missing’. Technique 3 included joints that were difficult to grade as an over estimated score. Radiographic OA prevalence was defined for the foot both collectively and separately for individual joints. Results When radiographs were scored using the LFA (Technique 1), radiographic foot OA was present in 89.9%. For Technique 2 the presence of radiographic foot OA was 83.5% and for Technique 3 it was 97.2%. At the individual joint level, using Technique 1, the presence of radiographic foot OA was higher with a wider range (18.3–74.3%) than Technique 2 (17.9–46.3%) and lower with a wider range (18.3–74.3%) than Technique 3 (39.9–79.4%). Conclusion The three different ways of interpreting the LFA scoring system when grading of individual joints is technically difficult and result in very different estimates of foot OA prevalence at both the individual joint and global foot level. Agreement on the best strategy is required to improve comparability between studies.

Abstract Background Research focusing on management of foot health has become more evident over the past decade, especially related to chronic conditions such as diabetes. The level of methodological rigour across this body of work however is varied and outputs do not appear to have been developed or translated into clinical practice. The aim of this systematic review was to assess the latest guidelines, standards of care and current recommendations relative to people with chronic conditions to ascertain the level of supporting evidence concerning the management of foot health. Methods A systematic search of electronic databases (Medline, Embase, Cinahl, Web of Science, SCOPUS and The Cochrane Library) for literature on recommendations for foot health management for people with chronic conditions was performed between 2000 and 2016 using predefined criteria. Data from the included publications was synthesised via template analysis, employing a thematic organisation and structure. The methodological quality of all included publications was appraised using the Appraisal for Research and Evaluation (AGREE II) instrument. A more in-depth analysis was carried out that specifically considered the levels of evidence that underpinned the strength of their recommendations concerning management of foot health. Results The data collected revealed 166 publications in which the majority (102) were guidelines, standards of care or recommendations related to the treatment and management of diabetes. We noted a trend towards a systematic year on year increase in guidelines standards of care or recommendations related to the treatment and management of long term conditions other than diabetes over the past decade. The most common recommendation is for preventive care or assessments (e.g. vascular tests), followed by clinical interventions such as foot orthoses, foot ulcer care and foot health education. Methodological quality was spread across the range of AGREE II scores with 62 publications falling into the category of high quality (scores 6–7). The number of publications providing a recommendation in the context of a narrative but without an indication of the strength or quality of the underlying evidence was high (79 out of 166). Conclusions It is clear that evidence needs to be accelerated and in place to support the future of the Podiatry workforce. Whilst high level evidence for podiatry is currently low in quantity, the methodological quality is growing. Where levels of evidence have been given in in high quality guidelines, standards of care or recommendations, they also tend to be strong-moderate quality such that further strategically prioritised research, if performed, is likely to have an important impact in the field.

Background: There is no good evidence to support the use of patient-reported outcome measures (PROMs) in setting preoperative thresholds for referral for hip and knee replacement surgery. Despite this, the practice is widespread in the NHS. Objectives/research questions: Can clinical outcome tools be used to set thresholds for hip or knee replacement? What is the relationship between the choice of threshold and the cost-effectiveness of surgery? Methods: A systematic review identified PROMs used to assess patients undergoing hip/knee replacement. Their measurement properties were compared and supplemented by analysis of existing data sets. For each candidate score, we calculated the absolute threshold (a preoperative level above which there is no potential for improvement) and relative thresholds (preoperative levels above which individuals are less likely to improve than others). Owing to their measurement properties and the availability of data from their current widespread use in the NHS, the Oxford Knee Score (OKS) and Oxford Hip Score (OHS) were selected as the most appropriate scores to use in developing the Arthroplasty Candidacy Help Engine (ACHE) tool. The change in score and the probability of an improvement were then calculated and modelled using preoperative and postoperative OKS/OHSs and PROM scores, thereby creating the ACHE tool. Markov models were used to assess the cost-effectiveness of total hip/knee arthroplasty in the NHS for different preoperative values of OKS/OHSs over a 10-year period. The threshold values were used to model how the ACHE tool may change the number of referrals in a single UK musculoskeletal hub. A user group was established that included patients, members of the public and health-care representatives, to provide stakeholder feedback throughout the research process. Results: From a shortlist of four scores, the OHS and OKS were selected for the ACHE tool based on their measurement properties, calculated preoperative thresholds and cost-effectiveness data. The absolute threshold was 40 for the OHS and 41 for the OKS using the preferred improvement criterion. A range of relative thresholds were calculated based on the relationship between a patient’s preoperative score and their probability of improving after surgery. For example, a preoperative OHS of 35 or an OKS of 30 translates to a 75% probability of achieving a good outcome from surgical intervention. The economic evaluation demonstrated that hip and knee arthroplasty cost of

Background: Shoulder dislocations are the most common joint dislocations seen in emergency departments. Most traumatic cases are anterior and cause recurrent dislocations. Management options include surgical and conservative treatments. There is a lack of evidence about which method is most effective after the first traumatic anterior shoulder dislocation (TASD). Objectives: To produce UK age- and sex-specific incidence rates for TASD. To assess whether or not surgery within 6 months of a first-time TASD decreases re-dislocation rates compared with no surgery. To identify clinical predictors of recurrent dislocation. Design: A population-based cohort study of first-time TASD patients in the UK. An initial validation study and subsequent propensity-score-matched analysis to compare re-dislocation rates between surgery and no surgery after a first-time TASD. Prediction modelling was used to identify potential predictors of recurrent dislocation. Setting: UK primary and secondary care data. Participants: Patients with a first-time TASD between 1997 and 2015. Interventions: Stabilisation surgery within 6 months of a first-time TASD (compared with no surgery). Stabilisation surgery within 12 months of a first-time TASD was also carried out as a sensitivity analysis. Main outcome measure: Re-dislocation rate up to 2 years after the first TASD. Methods: Eligible patients were identified from the Clinical Practice Research Datalink (CPRD) (1997–2015). Accuracy of shoulder dislocation coding was internally validated using the CPRD General Practitioner questionnaire service. UK age- and sex-specific incidence rates for TASD were externally validated against rates from the USA and Canada. A propensity-score-matched analysis using linked CPRD and Hospital Episode Statistics (HES) data compared re-dislocation rates for patients aged 16–35 years, comparing surgery with no surgery. Multivariable Cox regression models for predicting re-dislocation were developed for the surgical and non-surgical cohorts. Results: Shoulder dislocation was coded correctly for 89% of cases in the CPRD [95% confidence interval (CI) 83% to 95%], with a ‘primary’ dislocation confirmed for 76% of cases (95% CI 67% to 85%). Far fewer patients than expected received stabilisation surgery within 6 months of a first TASD, leading to an underpowered study. Around 20% of re-dislocation rates were observed for both surgical and non-surgical patients. The sensitivity analysis at 12 months also showed little difference in re-dislocation rates. Missing data on risk factors limited the value of the prediction modelling; however, younger age, epilepsy and sex (male) were identified as statistically significant predictors of re-dislocation. Limitations: Far fewer than the expected number of patients had surgery after a first-time TASD, resulting in an underpowered study. This and residual confounding from missing risk factors mean that it is not possible to draw valid conclusions. Conclusions: This study provides, for the first time, UK data on the age- and sex-specific incidence rates for TASD. Most TASD occurs in men, but an unexpected increased incidence was observed in women aged > 50 years. Surgery after a first-time TASD is uncommon in the NHS. Re-dislocation rates for patients receiving surgery after their first TASD are higher than previously expected; however, important residual confounding risk factors were not recorded in NHS primary and secondary care databases, thus preventing useful recommendations. Future work: The high incidence of TASD justifies investigation into preventative measures for young men participating in contact sports, as well as investigating the risk factors in women aged > 50 years. A randomised controlled trial would account for key confounders missing from CPRD and HES data. A national TASD registry would allow for a more relevant data capture for this patient group. Study registration: Independent Scientific Advisory Committee (ISAC) for the Medicines and Healthcare Products Regulatory Agency (ISAC protocol 15_0260). Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Although hip and knee arthroplasties are considered to be common elective cost-effective operations, up to one-quarter of patients are not satisfied with the operation. A number of risk factors for implant failure are known, but little is known about the predictors of patient-reported outcomes. Objectives: (1) Describe current and future needs for lower limb arthroplasties in the UK; (2) describe important risk factors for poor surgery outcomes and combine them to produce predictive tools (for hip and knee separately) for poor outcomes; (3) produce a Markov model to enable a detailed health economic analysis of hip/knee arthroplasty, and for implementing the predictive tool; and (4) test the practicality of the prediction tools in a pragmatic prospective cohort of lower limb arthroplasty. Design: The programme was arranged into four work packages. The first three work packages used the data from large existing data sets such as Clinical Practice Research Datalink, Hospital Episode Statistics and the National Joint Registry. Work package 4 established a pragmatic cohort of lower limb arthroplasty to test the practicality of the predictive tools developed within the programme. Results: The estimated number of total knee replacements (TKRs) and total hip replacements (THRs) performed in the UK in 2015 was 85,019 and 72,418, respectively. Between 1991 and 2006, the estimated age-standardised rates (per 100,000 person-years) for a THR increased from 60.3 to 144.6 for women and from 35.8 to 88.6 for men. The rates for TKR increased from 42.5 to 138.7 for women and from 28.7 to 99.4 for men. The strongest predictors for poor outcomes were preoperative pain/function scores, deprivation, age, mental health score and radiographic variable pattern of joint space narrowing. We found a weak association between body mass index (BMI) and outcomes; however, increased BMI did increase the risk of revision surgery (a 5-kg/m2 rise in BMI increased THR revision risk by 10.4% and TKR revision risk by 7.7%). We also confirmed that osteoarthritis (OA) severity and migration pattern of the hip predicted patient-reported outcome measures. The hip predictive tool that we developed performed well, with a corrected R2 of 23.1% and had good calibration, with only slight overestimation of Oxford Hip Score in the lowest decile of outcome. The knee tool developed performed less well, with a corrected R2 of 20.2%; however, it had good calibration. The analysis was restricted by the relatively limited number of variables available in the extant data sets, something that could be addressed in future studies. We found that the use of bisphosphonates reduced the risk of revision knee and hip surgery by 46%. Hormone replacement therapy reduced the risk by 38%, if used for at least 6 months postoperatively. We found that an increased risk of postoperative fracture was prevented by bisphosphonate use. This result, being observational in nature, will require confirmation in a randomised controlled trial. The Markov model distinguished between outcome categories following primary and revision procedures. The resulting outcome prediction tool for THR and TKR reduced the number and proportion of unsatisfactory outcomes after the operation, saving NHS resources in the process. The highest savings per quality-adjusted life-year (QALY) forgone were reported from the oldest patient subgroups (men and women aged ≥ 80 years), with a reported incremental cost-effectiveness ratio of around £1200 saved per QALY forgone for THRs. In the prospective cohort of arthroplasty, the performance of the knee model was modest (R2 = 0.14) and that of the hip model poor (R2 = 0.04). However, the addition of the radiographic OA variable improved the performance of the hip model (R2 = 0.125 vs. 0.110) and high-sensitivity C-reactive protein improved the performance of the knee model (R2 = 0.230 vs. 0.216). These data will ideally need replication in an external cohort of a similar design. The data are not necessarily applicable to other health systems or countries. Conclusion: The number of total hip and knee replacements will increase in the next decade. High BMI, although clinically insignificant, is associated with an increased risk of revision surgery and postoperative complications. Preoperative pain/function, the pattern of joint space narrowing, deprivation index and level of education were found to be the strongest predictors for THR. Bisphosphonates and hormone therapy proved to be beneficial for patients undergoing lower limb replacement. The addition of new predictors collected from the prospective cohort of arthroplasty slightly improved the performance of the predictive tools, suggesting that the potential improvements in both tools can be achieved using the plethora of extra variables from the validation cohort. Although currently it would not be cost-effective to implement the predictive tools in a health-care setting, we feel that the addition of extensive risk factors will improve the performances of the predictive tools as well as the Markov model, and will prove to be beneficial in terms of cost-effectiveness. Future analyses are under way and awaiting more promising provisional results. Future work: Further research should focus on defining and predicting the most important outcome to the patient. Funding: The National Institute for Health Research Programme Grants for Applied Research programme.

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies.

Background: Professional bodies have produced comprehensive guidance about the management of hip fracture. They recommend orthogeriatric services focusing on achieving optimal recovery, and fracture liaison services (FLSs) focusing on secondary fracture prevention. Despite such guidelines being in place, there is significant variation in how services are structured and organised between hospitals. Objectives: To establish the clinical effectiveness and cost-effectiveness of changes to the delivery of secondary fracture prevention services, and to identify barriers and facilitators to changes. Design: A service evaluation to identify each hospital’s current models of care and changes in service delivery. A qualitative study to identify barriers and facilitators to change. Health economics analysis to establish NHS costs and cost-effectiveness. A natural experimental study to determine clinical effectiveness of changes to a hospital’s model of care. Setting: Eleven acute hospitals in a region of England. Participants: Qualitative study – 43 health professionals working in fracture prevention services in secondary care. Interventions: Changes made to secondary fracture prevention services at each hospital between 2003 and 2012. Main outcome measures: The primary outcome is secondary hip fracture. Secondary outcomes include mortality, non-hip fragility fracture and the overall rate of hip fracture. Data sources: Clinical effectiveness/cost-effectiveness analyses – primary hip fracture patients identified from (1) Hospital Episode Statistics (2003–13, n = 33,152); and (2) Clinical Practice Research Datalink (1999–2013, n = 11,243). Results: Service evaluation – there was significant variation in the organisation of secondary fracture prevention services, including staffing levels, type of service model (consultant vs. nurse led) and underlying processes. Qualitative – fracture prevention co-ordinators gave multidisciplinary health professionals capacity to work together, but communication with general practitioners was challenging. The intervention was easily integrated into practice but some participants felt that implementation was undermined by under-resourced services. Making business cases for a service was particularly challenging. Natural experiment – the impact of introducing an orthogeriatrician on 30-day and 1-year mortality was hazard ratio (HR) 0.73 [95% confidence interval (CI) 0.65 to 0.82] and HR 0.81 (95% CI 0.75 to 0.87), respectively. Thirty-day and 1-year mortality were likewise reduced following the introduction or expansion of a FLS: HR 0.80 (95% CI 0.71 to 0.91) and HR 0.84 (95% CI 0.77 to 0.93), respectively. There was no significant impact on time to secondary hip fracture. Health economics – the annual cost in the year of hip fracture was estimated at £10,964 (95% CI £10,767 to £11,161) higher than the previous year. The annual cost associated with all incident hip fractures in the UK among those aged ≥ 50 years (n = 79,243) was estimated at £1215M. At a £30,000 per quality-adjusted life-year threshold, the most cost-effective model was introducing an orthogeriatrician. Conclusion: In hip fracture patients, orthogeriatrician and nurse-led FLS models are associated with reductions in mortality rates and are cost-effective, the orthogeriatrician model being the most cost-effective. There was no evidence for a reduction in second hip fracture. Qualitative data suggest that weaknesses lie in treatment adherence/monitoring, a possible reason for the lack of effectiveness on second hip fracture outcome. The effectiveness on non-hip fracture outcomes remains unanswered. Future work: Reliable estimates of health state utility values for patients with hip and non-hip fractures are required to reduce uncertainty in health economic models. A clinical trial is needed to assess the clinical effectiveness and cost-effectiveness of a FLS for non-hip fracture patients. Funding: The National Institute for Health Research (NIHR) Health Services and Delivery Research programme and the NIHR Musculoskeletal Biomedical Research Unit, University of Oxford.

Table of content P3 Medial longitudinal arch development of school children Jasper W.K. Tong, Veni P. Kong P4 Is measuring the subtalar joint reliable? Lily Sze, Susie Gale, John Veto, Carla McArdle P5 Comparison of turning gait biomechanics between able‐bodied and unilateral transtibial amputee participants Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P6 Comparison of walking gait biomechanics between able‐bodied and unilateral transtibial amputee participants using a new model of energy‐storage‐and‐return (ESAR) prosthetic Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P7 An observational study of in‐shoe plantar and dorsal pressures of skilled downhill skiers on a dry ski slope Robert Ashford, Roozbeth Naemi, Nachiappan Chocklingam, Xavi de Blasc P8 If the shoe fits: a footwear choice toolkit informed by social science methodologies Lisa Farndon, Vicki Robinson, Emily Nicholls P9 The identification of emotions from gait Tabitha Birch, Ivan Birch P11 Experience of foot problems in patients with systemic lupus erythematosus Simon Otter, Sunil Kumar, Peter Gow, Nicola Dalbeth, Michael Corkill, Kevin Davies, Sam Panthakalam, Maheswaran Rohan, Keith Rome P14 Negative pressure wound therapy for the management of foot wounds in the diabetic population: a review of the literature Chloe Egan, Lisa Chandler P15 Lower limb vascular assessment in diabetes: a multifaceted assessment of objective screening techniques Peta Tehan, Vivienne Chuter, Jennifer Sonter, Sean Lanting P16 Improving outcomes for diabetes foot complications Lorna Hicks P17 Acupuncture… an alternative or adjunctive treatment option for diabetes‐related neuropathic pain? Christopher Joyce, David Watterson, Caroline McIntosh P18 “My back is in agony” – A cross‐sectional study into the relationship between musculoskeletal complaints and a whole body postural risk assessment in podiatry students Christopher Joyce, Nigel Roberts P19 Swabs of the treatment couches: Does the material type and texture of podiatric treatment couches increase microorganism contamination? Jacqueline Forss, Chrystalla Charalambous, Jack Kirby, Oluwakemi Ojo P20 Does increased exudate viscosity effect the absorption rate of exudate into four different wound dressings? Jacqueline Forss, Sarah Caukill, Jacqueline Capon, Radiance Fong, Louis Loy P21 An investigation into the microbial load of a 40 °C and 60 °C wash Matthew Diment, Madeleine Murray, Mairghread Ellis, Carla McArdle P23 The sensitivity and specificity of the toe brachial index in detecting peripheral arterial disease: a systematic review and meta‐analysis Peta Tehan, Vivienne Chuter, Christopher Oldmeadow P24 Medicines management activities and non‐medical prescribing within podiatry and physiotherapy: an integrative review of the literature Nicola Carey, Karen Stenner, Heather Gage, Jane Brown, Peter Williams, Simon Otter, Ann Moore, Jude Edwards, Freda Mold, Molly Courtenay A7.2 Non‐invasive vascular assessment in the foot with Diabetes: Diagnostic accuracy of ankle brachial index, toe brachial index and continuous wave Doppler Peta Tehan, Alan Bray, Vivienne Chuter A7.5 The efficacy of dressings on post nail surgery phenolised wounds Pamela Hindmoor B7.1 Cross‐sectional study investigating the role of proximal and distal factors in the development of patellofemoral joint pain Craig Gwynne, Sarah Curran B7.2 Podiatrist's interpretation and use of evidence in MSK practice Andy Bridgen B7.4 Predictors of falling in older podiatry patients – findings from the REFORM study Caroline Fairhurst, Dr Joy Adamson, Belen Corbacho Martin, Sarah Cockayne, Prof Catherine Hewitt, Kate Hicks, Anne‐Maree Keenan, Lorraine Loughrey‐Green, Hylton Menz, Anthony Redmond, Sara Rodgers, Jude Watson, David Torgerson, Robin Hull, Sarah Lamb, Caroline McIntosh, Wesley Vernon, Lisa Farndon B7.5 The REFORM study: Insole preference, requirements and compliance of podiatry patient's aged 65 and over and at risk of falling Lorraine Loughrey‐Green, Sarah Cockayne, Anthony Redmond, Anne‐Maree Keenan, Sara Rodgers, Lisa Farndon, Wesley Vernon, David Torgerson, Caroline Fairhurst, Jude Watson, Hylton Menz, Sarah Lamb, Robin Hull B7.6 A podiatry intervention to reduce falls in care home residents is feasible and demonstrates benefits: results from PIRFECT, a feasibility randomised controlled trial Gavin Wylie, Zoe Young, Brian Williams, Frank Sullivan, Hylton Menz, Simon Ogston, Jacqui Morris C7.1 A survey exploring footwear habits in people with stroke and people with Parkinson's Cathy Bowen, Dorit Kunkel, Mark Cole, Margaret Donovan‐Hall, Ruth Pickering, Malcolm Burnett, Dan Bader, Judy Robison, Louis Mamode, Ann Ashburn C7.2 Painful foot osteoarthritis; a common symptom in a common pathology? Peter McQueen, Maxine Daniels, Michael Doherty, Nigel Arden, Cathy Bowen C7.4 Clinical diagnosis of symptomatic forefoot neuroma in the general population: Delphi based recommendations Charlotte Dando, Lindsey Cherry, Cathy Bowen C7.5 The development and implementation of a Clinical Quality Improvement Framework suitable for use in community services Nichola Stefanou C7.6 The REFORM study ‐ methodological considerations in running a cohort randomised controlled trial within a podiatry patient caseload Sarah Cockayne, Joy Adamson, Caroline Fairhurst, Catherine Hewitt, Anne‐Maree Keenan, Sally Lamb, Lorraine Loughrey‐Green, Caroline McIntosh, Hylton Menz, Anthony Redmond, Sara Rodgers, Wesley Vernon, Jude Watson, Lisa Farndon, Belen Corbacho, Robin Hull, David Torgerson A31 Jewel in the crown: Exploring the factors contributing to the development and impact of foot problems in Systemic Sclerosis (SSc) Begonya Alcacer‐Pitarch, Anthony Redmond, Maya Buch, Anne‐Maree Keenan

A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.Study participants were derived from the Chingford study. Kellgren-Lawrence (KL) grades and the individual features of osteophytes and joint space narrowing (JSN) were scored from radiographs of hands, knees, hips, and lumbar spines. The total KL score, osteophyte score, and JSN score were calculated and used as indicators of the total burden of radiographic OA. Forty-one common SNPs within SMAD3 were genotyped using the Illumina HumanHap610Q array. Linear regression modelling was used to test the association between the total KL score, osteophyte score, and JSN score and each of the 41 SNPs, with adjustment for patient age and BMI. Permutation testing was used to control the false positive rate.A total of 609 individuals were included in the analysis. All were Caucasian females with a mean age of 60.9±5.8. We found that rs3825977, with a minor allele (T) frequency of 20%, in the last intron of SMAD3, was significantly associated with total KL score (β = 0.14, Ppermutation = 0.002). This association was stronger for the total JSN score (β = 0.19, Ppermutation = 0.002) than for total osteophyte score (β = 0.11, Ppermutation = 0.02). The T allele is associated with a 1.47-fold increased odds for people with 5 or more joints to be affected by radiographic OA (Ppermutation = 0.046).We found that SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association.

BackgroundObesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.Methods and findingsWe used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores).ConclusionsOn the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.