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Background: A relation between provider volume and outcome of total joint replacement (TJR) has not been demonstrated in Canada. Given the recent increase in TJR, changing patient characteristics and small sizes of previous Ontario studies, we reassessed whether adverse outcomes of TJR are related to hospital and surgeon procedure volumes.Methods: We included all Ontarians aged 20 years and older who underwent a unilateral elective primary total hip replacement (THR) or total knee replacement (TKR) between April 2000 and March 2004. The main data sources were hospital discharge abstracts and physician billings. We defined provider volume as the average annual number of primary and revision procedures performed by hospitals and surgeons during the study period. We assessed the association between procedure volumes and acute length of hospital stay (ALOS) and between volume and rate of surgical complications during the index admission; death within 90 days of operation; readmission for amputation, fusion or excision within 1 year; and revision arthroplasty within 1 year. We adjusted for age, sex, comorbidity, arthritis type, teaching hospital status and discharge disposition. The analyses of hospital volume were adjusted for surgeon volume and vice versa.Results: We included 20,290 patients who received THR and 27,217 who received TKR. Patient age, sex and comorbidity were significant predictors of complications and mortality. There were no associations between provider volume and mortality. Findings for other outcomes were mixed. Surgeon procedure volume was related to rates of revision THR but not to rates of revision TKR. Shorter ALOS was associated with male sex, younger age, fewer comorbidities, discharge to a rehabilitation unit or facility and greater surgeon volume.Conclusion: Patient characteristics were significant predictors of complications, ALOS and mortality after primary TJR. Evidence for a relation between provider volume and outcome was limited and inconsistent. [ABSTRACT FROM AUTHOR]

Background: The best measure of body habitus as a risk factor for chronic disease is not well defined. Our intent was to examine the relation between waist-hip ratio (WHR) and body mass index (BMI) as a measurement of body habitus in patients with end-stage knee osteoarthritis (OA).Methods: We reviewed the data of 200 consecutive patients in our registry undergoing knee replacement surgery for demographic data of age, sex, BMI and WHR. We performed a stratified analysis by sex and calculated the risk ratios (RRs) to describe the risk of being classified as obese by WHR for those considered obese by the BMI criteria.Results: A similar percentage of male and female patients were classified as obese by the BMI criteria (38% v. 42%, respectively). Men were classified as obese more often than women by WHR (92% v. 82%). The RR of being obese as determined by WHR if classified as obese by the BMI criteria was 1.04 (95% confidence interval [CI]0.91-1.18) for men and 1.23 (95% CI 1.03-1.46) for women.Conclusion: Among patients with knee OA, the overlap between BMI and WHR is greater in women than men. This difference has implications for defining the prevalence of metabolic syndrome in this population. [ABSTRACT FROM AUTHOR]

Background: Most joint-replacement surgeries are currently performed in community hospitals. We sought to determine whether the functional outcomes of joint-replacement surgery differ between academic and community hospitals.Methods: We surveyed 471 patients for demographic data, Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores and Medical Outcomes Study Short Form 36 (SF-36) scores at baseline and at 3-month and 1-year follow-up. We assessed patient satisfaction at 1 year with a single survey question.Results: Community hospital patients (n = 269) were significantly older and had greater comorbidity than academic hospital patients (n = 202; p < 0.05). We found no difference in WOMAC scores, SF-36 scores or in patient satisfaction between hospitals at 1-year follow-up (p > 0.05). Adjusted analysis showed that patients undergoing surgery in an academic or community hospitals have the same functional outcomes.Conclusion: There is no significant difference in the functional outcomes of joint-replacement surgery between academic and community hospitals. Further work will involve evaluating cost of care differences between these types of hospitals. [ABSTRACT FROM AUTHOR]

Background: Total joint arthroplasty is a highly efficacious and cost-effective procedure for moderate to severe arthritis in the hip and knee. Although patient characteristics are considered to be important determinants of who receives total joint arthroplasty, no systematic review has addressed how they affect the outcomes of total joint arthroplasty. This study addresses how patient characteristics influence the outcomes of hip and knee arthroplasty in patients with osteoarthritis.Methods: We searched 4 bibliographic databases (MEDLINE 1980-2001, CINAHL 1982-2001, EMBASE 1980-2001, HealthStar 1998-1999) for studies involving more than 500 patients with osteoarthritis and 1 or more of the following outcomes after total joint arthroplasty: pain, physical function, postoperative complications (short-and long-term) and time to revision. Prognostic patient characteristics of interest included age, sex, race, body weight, socioeconomic status and work status.Results: Sixty-four of 14,276 studies were eligible for inclusion and had extractable data. Younger age (variably defined) and male sex increased the risk of revision 3-fold to 5-fold for hip and knee arthroplasty. The influence of weight on the risk of revision was contradictory. Mortality was greatest in the oldest age group and among men. Function for older patients was worse after hip arthroplasty (particularly in women). Function after knee arthroplasty was worse for obese patients.Conclusion: Although further research is required, our findings suggest that, after total joint arthroplasty, younger age and male sex are associated with increased risk of revision, older age and male sex are associated with increased risk of mortality, older age is related to worse function (particularly among women), and age and sex do not influence the outcome of pain. Despite these findings, all subgroups derived benefit from total joint arthroplasty, suggesting that surgeons should not restrict access to these procedures based on patient characteristics. In addition, future research needs to provide standardized measures of outcomes. [ABSTRACT FROM AUTHOR]

Objective: Increased wait times for total joint arthroplasty (TJA) are a concern nationally and provincially. Additionally, the number of patients requiring revision of their initial TJA is increasing. The purpose of this study was to evaluate the wait times and impact of waiting for revision TJA.Methods: We followed 127 revision hip arthroplasty patients (mean age 68 y) prospectively while they waited for surgery. We collected Western Ontario and McMaster Universities Osteoarthritis Index (pain, stiffness and physical function) data at the decision for surgery and at 6-month intervals until surgery.Results: The mean wait time for surgery was 123.8 days (mean wait times for individual surgeons ranged from 7 to 213 d). Of the patients, 106 waited < 6 months, 12 waited 6-12 months and 9 waited > 12 months. Wait times evaluated up to 6 months, 6-12 months or > 12 months demonstrated significant increases in pain (F = 7.12, p = 0.01), with a mean change of 2.6 points when patients waited > 6 months. Physical disability increased (F = 4.61, p = 0.01), with a mean change of 5.1 points when the wait time was 6-12 months and 8.8 points when the wait time was > 12 months.Conclusion: Waiting > 6 months for revision hip arthroplasty resulted in significant increases in pain and physical disability. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the association between procedure volume and patient-centered outcomes such as functional status. METHODS: We performed an observational study of a stratified random sample of Medicare beneficiaries who underwent primary total knee replacement (TKR) in 2000. Low-volume surgeons were defined as surgeons performing < or =6 TKRs per year in the Medicare population, and low-volume centers were defined as those in which < or =25 TKRs per year were performed. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) functional status score (0-100 scale; 100 = best) 2 years after TKR. We defined a WOMAC functional status score of <60 as a poor functional outcome. Analyses were adjusted for sociodemographic factors, preoperative functional status, and comorbidities. RESULTS: Fifty-eight percent of 1,597 eligible patients agreed to participate. Twelve percent of participating patients had a WOMAC score <60 2 years following TKR. Patients operated upon by low-volume surgeons in low-volume hospitals were twice as likely to have a poor WOMAC functional status score as patients operated upon by higher volume surgeons and in higher volume hospitals (odds ratio 2.1, 95% confidence interval 1.1-4.2). CONCLUSION: Patients operated upon in low-volume hospitals by low-volume surgeons had worse functional outcomes 2 years after TKR. These findings add a new and important dimension to the discussion of whether to promote selective referral of procedures such as TKR to high-volume centers. [ABSTRACT FROM AUTHOR]

Few studies have examined diabetes impact on total joint arthroplasty (TJA) outcomes, with variable findings. We investigated the association between diabetes and post-TJA physical function and pain, examining whether diabetes impact differs by sex and BMI. Patient sample completed questionnaires within 3 months prior to hip or knee TJA for osteoarthritis (OA) and 1-year post-surgery. Surgical 'non-response' was defined as < 30% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function at 1-year. Two adjusted logistic regression models were estimated: (1) excluding, (2) including an interaction between diabetes, sex and BMI. The sample (626 hip, 754 knee) was 54.9% female, had mean BMI of 30.1, 13.0% reported diabetes. In adjusted models excluding an interaction, diabetes was not associated with non-response. However, a significant 3-way interaction (physical function: p = 0.003; pain: p = 0.006) between diabetes, sex, and BMI was found and was associated with non-response: non-response probability increased with increasing BMI in men with diabetes, but decreased with increasing BMI in women in diabetes. Findings suggest uncertainty in diabetes impact may be due to differential impacts by sex and BMI. A simple consideration of diabetes as present vs. absent may not be sufficient, with implications for the large TJA population., (© 2024. The Author(s).)

Objective: We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA)., Methods: Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching., Results: The matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7-25.8), function (MD 21.2; 95% CI 17.7-24.4), and quality of life (MD 18.3; 15.0-21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA., Conclusion: TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed., (© 2024 American College of Rheumatology.)

Objective: To assess the impact of diabetes on physical and mental health status, as well as patient satisfaction, one-year following knee and hip total joint arthroplasty (TJA) for osteoarthritis (OA)., Methods: Participants were 626 hip and 754 knee TJA patients. Pre-surgery data were collected on socio-demographics and health status. The 12-item Short Form Health Survey (SF-12) was collected pre- and one year post-surgery, and physical (PCS) and mental component (MCS) summary scores computed. One-year patient satisfaction was also recorded. Four regression models tested the effect of diabetes on: 1) PCS change score; 2) MCS change score; 3) achieving minimal clinically important improvement (MCII) on PCS; and 4) patient satisfaction ('Somewhat or Very Satisfied' vs. 'Somewhat or Very Dissatisfied'). An interaction between surgical joint and diabetes was tested in each model., Results: Self-reported diabetes prevalence was 13.0% (95% CI: 11.2%-14.7%) and was more common in knee 16.1% (95% CI: 13.4%-18.7%) than hip 9.3% (95% CI: 7.0%-11.5%) patients. In adjusted analyses, change scores were 2.3 units less on the PCS for those with diabetes compared to those without (p = 0.005). Patients with diabetes were about half as likely to achieve MCII as patients without diabetes (p = 0.004). Diabetes was not significantly associated with satisfaction or changes in MCS scores. Diabetes effects did not differ by surgical joint., Conclusions: Findings support that diabetes has a negative impact on improvements in physical health after TJA. Considering the growing prevalence of OA and diabetes in the population, our findings support the importance of perioperative screening and management of diabetes in patients undergoing TJA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Power et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries., Methods: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors., Results: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs., Conclusions: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms., Methods: Two independent cohorts from St John's, NL, Canada (n = 430), and Toronto, ON, Canada (n = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts., Results: One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P < 2 × 10-5), were significantly associated with sustained knee pain., Conclusions: Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m 2 , and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10 -4 ), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice's weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Objective: Multiple disease phenotypes have been identified in knee osteoarthritis (OA) patients based on anthropometric, sociodemographic and clinical factors; however, differential systemic metabolite-based signatures in OA patients are not well understood. We sought to identify differential plasma metabolome signatures in a cross-sectional sample of late-stage knee OA patients., Methods: Plasma from 214 (56.5% female; mean age ​= ​67.58 years) non-diabetic, non-obese (BMI <30 ​kg/m 2 , mean ​= ​26.25 ​kg/m 2 ), radiographic KL 3/4 primary knee OA patients was analyzed by metabolomics. Patients with post-traumatic OA and rheumatoid arthritis were excluded. Hierarchical clustering was used to identify patient clusters based on metabolite levels. A refined metabolite signature differentiating patient clusters was determined based on ≥ 10% difference, significance by FDR-adjusted t -test (q-value < 0.05), and random forests importance score ≥1, and analyzed by AUROC. Bioinformatics analysis was used to identify genes linked to ≥2 annotated metabolites. Associated enriched pathways (q ​< ​0.05) were determined., Results: Two patient clusters were determined based on the levels of 151 metabolites identified. Metabolite signature refinement found 24 metabolites could accurately predict cluster classification within the sample (AUC ​= ​0.921). Fifty-six genes were linked to at least 2 ​KEGG annotated metabolites. Pathway analysis found 26/56 genes were linked to enriched pathways including tRNA acylation and B-vitamin metabolism., Conclusion: This study demonstrates systemic metabolites can classify a cross-sectional cohort of OA patients into distinct clusters. Links between metabolites, genes and pathways can help determine biological differences between OA patients, potentially improving precision medicine and decision-making., Competing Interests: The authors declare no conflicts of interest related to this manuscript., (© 2022 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI).)

Objective: MicroRNA-34a-5p (miR-34a-5p) expression is elevated in the synovial fluid of patients with late-stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR-34a-5p in OA pathogenesis., Methods: Expression of miR-34a-5p was determined in joint tissues and human plasma (n = 71). Experiments using miR-34a-5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast-like synoviocytes (FLS) (n = 7-9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high-fat diet and subjected to DMM (n = 11). Wild-type (WT) mice (n = 9) and miR-34a-knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t-test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes., Results: Expression of miR-34a-5p was significantly increased in the plasma, cartilage, and synovium of patients with late-stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR-34a-5p expression was significantly increased in obese patients with late-stage OA, and in the plasma and knee joints of mice fed a high-fat diet. In human OA chondrocytes and FLS, miR-34a-5p mimic increased key OA pathology markers, while miR-34a-5p ASO improved cellular gene expression. Intraarticular miR-34a-5p mimic injection induced an OA-like phenotype. Conversely, miR-34a-5p ASO injection imparted cartilage-protective effects in the DMM and high-fat diet/DMM models. The miR-34a-KO mice exhibited protection against DMM-induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR-34a-5p signaling network., Conclusion: Our findings provide comprehensive evidence of the role and therapeutic potential of miR-34a-5p in OA., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The influence of sex on post-total knee arthroplasty (TKA) outcomes has been variable in the literature. Though sex is often reported as an averaged effect, we undertook this study to investigate whether sex modified the influence of presurgery characteristics on post-TKA knee pain., Methods: This was a prospective study with data derived from 477 TKA osteoarthritis patients (279 women, 198 men). Questionnaires were completed presurgery and at 3 months postsurgery. The association between 3-month post-TKA knee pain and presurgery covariates (body mass index, comorbidity count, symptomatic joint count, low back pain, knee pain, and depressive symptoms) was assessed by linear regression. Sex-specific effects were evaluated using interactions., Results: Women had significantly worse presurgery knee pain, joint count, and depressive symptoms, and worse postsurgery knee pain, than men. With simple covariate adjustment, no sex effect on pain was found. However, sex was found to moderate the effects of comorbidities (worse for women [P = 0.013]), presence of low back pain (worse for men [P = 0.003]), and depressive symptoms (worse for men [P < 0.001]) on postsurgery pain. Worse presurgery pain was associated with worse postsurgery pain similarly for women and men., Conclusion: The influence of some patient factors on early post-TKA pain cannot be assumed to be the same for women and men; average effects may mask underlying associations. Results suggest a need to consider sex differences in understanding TKA outcomes, which may have important implications for prognostic tool development in TKA., (© 2019, American College of Rheumatology.)

Objective: To evaluate rates of prescription opioid use among patients with presurgical knee, hip, and spine osteoarthritis (OA) and associations between use and sociodemographic and health status characteristics., Methods: Participants were patients with presurgical, end-stage OA of the knee (n = 77), hip (n = 459), and spine (n = 168). Data were collected on current use of opioids and other pain medications, as well as measures of sociodemographic and health status variables and depression and pain (0-10 numeric rating scale). Rates of opioid use were calculated by sex, age, and surgical site. Multivariable logistic regression was used to examine associations between opioid use (sometimes/daily versus never) and other study variables., Results: The mean age of participants was 65.6 years; 55.5% were women, 15% of patients reported "sometimes" using opioids, and 15% reported "daily use." Use of opioids was highest among patients with spine OA (40%) and similar among patients with knee and hip OA (28% and 30%, respectively). Younger women (ages <65 years) reported the greatest use of opioids overall, particularly among patients with spine OA. From multivariable logistic regression, greater likelihood of opioid use was significantly associated with spine OA (versus knee OA), obesity, being a current or former smoker, higher symptomatic joint count, greater depressive symptoms, greater pain, and current use of other prescription pain medication., Conclusion: Nearly one-third of patients with presurgical OA used prescription opioid medication. Given the questionable efficacy of opioids in OA and risk of adverse effects, higher opioid use among younger individuals and those with depressive symptoms is of concern and warrants further investigation., (© 2019, American College of Rheumatology.)

Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM-MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient-reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast-enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM-MSCs were characterized by a panel of anti-inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro-inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM-MSC anti-inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM-MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM-MSC dosing and BM-MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Objective: To examine patterns of depressive symptoms before and over the year following osteoarthritis (OA) surgery, stratified by joint and postsurgical outcome., Methods: Participants were hip (n = 287), knee (n = 360), and lumbar spine (n = 100) OA patients scheduled for joint replacement or decompression surgery with or without fusion. One pre- and 4 postsurgery questionnaires were completed. Depressive symptoms were quantified using the Hospital Anxiety and Depression Scale (HADS). One-year outcomes were based on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores for hip and knee patients and Oswestry Disability Index (ODI) scores for spine patients and were categorized as "worse" (top score tertile) vs. "better" outcomes (first, second tertiles). Plots over time were generated by joint and outcome: 1) mean pain/disability and depression scores and 2) percentage of patients meeting HADS cut-off for depression "caseness," reporting depression diagnosis and treatment., Results: There were notable decreases in depression scores for patients with better outcomes. For those with worse outcomes, decreases were smaller for hip patients and were not significant for knee and spine patients. Among those with poorer outcomes, 25% of spine and knee patients were depression "cases" pre- and postsurgery; an additional 16% of spine and 10% of knee patients developed new "caseness" postsurgery. The proportion of these patients deemed depression cases by score was much higher than the proportion reporting diagnosis/treatment., Conclusion: Although depressive symptoms decrease overall in OA patients postsurgery, degrees of change vary by joint and surgical outcome. Greater attention to mental health postsurgery is warranted and may lead to improved surgical outcomes, particularly among knee and spine patients., (© 2019 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: Chronic, low-grade inflammation of the synovium (synovitis) is a hallmark of osteoarthritis (OA), thus understanding of OA immunobiology, mediated by immune effectors, is of importance. Specifically, monocytes/macrophages (MΦs) are known to be abundantly present in OA joints and involved in OA progression. However, different subsets of OA MΦs have not been investigated in detail, especially in terms of their relationship with patient-reported outcome measures (PROMs). We hypothesized that levels of synovial fluid (SF) MΦ subsets are indicative of joint function and quality of life in patients with OA, and can therefore serve as biomarkers and therapeutic targets for OA., Methods: In this cohort study, synovial fluid leukocytes (SFLs, N = 86) and peripheral blood mononuclear cells (n = 53) from patients with knee OA were characterized. Soluble MΦ receptors and chemokine (sCD14, sCD163, CCL2, CX3CL1) levels were detected in SF using immunoassays. Linear models, adjusted for sex, age and body mass index, were used to determine associations between SF MΦs and soluble factors with PROMs (N = 83). Pearson correlation was calculated to determine correlation between MΦ subsets, T cells and soluble factors., Results: SF MΦs were the most abundant SFLs. Within these, the double-positive CD14 + CD16 + -MΦ subset is enriched in knee OA SF compared to the circulation. Importantly, MΦ subset ratios correlated with PROMs, specially stiffness, function and quality of life. Interestingly, the SF CD14 + CD16 + -MΦ subset ratio correlated with SF chemokine (C-C motif) ligand 2 (CCL2) levels but not with levels of sCD163 or sCD14; we found no association between PROMs and either SF CCL2, sCD163, sCD14 or CX3CL1 (which was below detection levels). All SF MΦs displayed high levels of HLA-DR, suggesting an activated phenotype. Correlation between OA SF MΦ subsets and activated CD4 + T cell subsets suggests modulation of CD4 + T cell activation by MΦs., Conclusion: SF MΦ subsets are associated with knee OA PROMs and display an activated phenotype, which may lead to modulation of CD4 + T cell activation. Knee OA SF MΦ subsets could serve as knee OA function biomarkers and as targets of novel therapeutics.

Objective: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA)., Design: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country., Results: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA., Conclusion: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: It has been suggested that total knee replacement is being performed in people with less-severe osteoarthritis. We aimed to determine whether there were differences in the presurgery profile, symptoms and disability of 2 cohorts who underwent total knee replacement over a 10-year period., Methods: Patients aged 18-85 years undergoing primary total knee replacement for osteoarthritis at 1 of 4 sites in Toronto and Strathroy, Ontario, were recruited in a cohort study during 2006-2008 (cohort 1) and 2012-2015 (cohort 2). Patients undergoing unicompartmental or revision arthroplasty were excluded. Demographic and health (body mass index [BMI], comorbidity) variables and osteoarthritis severity, as assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the disability component of the Late-Life Function and Disability Instrument (LLFDI-D), were collected before surgery. We calculated proportions, means and standard deviations with 95% confidence intervals (CIs) for all data. We constructed density plots by tertile score for the WOMAC pain and physical function subscales and the LLFDI-D limitation scale., Results: There were 494 patients in cohort 1 and 251 patients in cohort 2. There were no differences in age, sex, education, living status, BMI, comorbidity, pain severity or disability between the cohorts based on overlapping 95% CIs and the density plots. More patients in cohort 1 than in cohort 2 were single (176 [35.6%], 95% CI 32.5%-41.1% v. 63 [25.1%], 95% CI 20.3%-31.0%). Patients in cohort 2 reported less limitation in higher-demand activities than did those in cohort 1 (mean score on LLFDI-D 62.3 [95% CI 60.7-63.9] v. 59.2 [95% CI 58.2-60.2])., Interpretation: The patient profile and reported osteoarthritis severity were similar in 2 cohorts that had total knee replacement over a 10-year period. This suggests that increasing total knee replacement volumes over this period likely were not driven by these factors., Competing Interests: Competing interests: Rajiv Gandhi reports institutional research support received from Smith & Nephew and Zimmer Biomet. No other competing interests were declared., (Copyright 2018, Joule Inc. or its licensors.)

Objective: We investigated whether pain at rest and pain on activity were differentially associated with neuropathic pain scores in individuals with end-stage hip and knee OA., Design: Study participants were 843 patients with hip or knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires, measures of socio-demographics, health status, medication use, neuropathic pain (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear regression models were estimated for men and women separately to examine the association between neuropathic pain scores (outcome) and study measures, entered in blocks., Results: Sample mean age was 65.1 years (SD: 9.6); 57.1% were women. Mean painDETECT scores were significantly higher (P ≤ֹ 0.001) for women (11.2 ± 6.6 out of 38) than men (9.3 ± 7.0), with 35.6% of women and 27.7% of men meeting cut-offs for possible or likely neuropathic pain. In the final regression model for women, the coefficients for both types of pain were statistically significant, although the coefficient for pain at rest was 1.6 times greater than that for pain on activity. For men, only pain at rest was significantly associated with neuropathic pain scores., Conclusions: Findings support that possible neuropathic pain is experienced by a notable proportion of patients with end-stage hip and knee OA and is more strongly associated with pain at rest than pain on activity, particularly in men. Clinical presentation of pain at rest may warrant more thorough evaluation for potential neuropathic pain and have implications for appropriate pain management., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Metabolic changes induced by high fat diet (HFD) that contribute to osteoarthritis (OA) are poorly understood. We investigated longitudinal changes to metabolites and their contribution to OA pathogenesis in response to HFD. HFD-fed mice exhibited acceleration of spontaneous age-related and surgically-induced OA compared to lean diet (LD)-fed mice. Using metabolomics, we identified that HFD-fed mice exhibited a distinct and sustained plasma metabolite signature rich in phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPCs), even after resumption of normal chow diet. Using receiver operator curve analysis and prediction modelling, we showed that the concentration of these identified metabolites could efficiently predict the type of diet and OA risk with an accuracy of 93%. Further, longitudinal evaluation of knee joints of HFD- compared to LD- fed mice showed a greater percentage of leptin-positive chondrocytes. Mechanistic data showed that leptin-treated human OA chondrocytes exhibited enhanced production of lysoPCs and expression of autotaxin and catabolic MMP-13. Leptin-induced increased MMP13 expression was reversed by autotaxin inhibition. Together, this study is the first to describe a distinct and sustained HFD-induced metabolite signature. This study suggests that in addition to increased weight, identified metabolites and local leptin-signaling may also contribute in part, towards the accelerated OA-phenotype observed in HFD mice.

Objective: We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex., Design: Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested., Results: Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P < 0.01; 4+ joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4 mg/l vs 9.3, P = 0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P < 0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men., Conclusions: There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to identify circulating microRNA (miRNA) signatures in knee synovial fluid (SF) from early-stage and late-stage knee osteoarthritis (OA) patients., Methods: miRNAs were screened by miRNA-PCR-arrays and validated by Real-time quantitative polymerase chain reaction (RT-qPCR) in SF from early-stage (Kellgren-Lawrence (KL): Grade: I/II) and late-stage OA patients (Grade: III/IV). OA cartilage or synovial explants were cultured to study the source/release of identified miRNAs. Computational-approach was utilized to predict gene/pathway targets., Results: Our screening/validation analysis identified a panel of seven (out of 752) circulating miRNAs (23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 34a-5p and 186-5p) that were significantly differentially expressed in late-stage vs early-stage OA-SF, irrespective of age, gender and Body Mass Index (BMI). miR-378a-5p was mostly detectable in majority of late-stage OA-SF. Cartilage explants stimulated with IL-1β showed a significant reduction in miR-23a-3p, 27a-3p and 27b-3p expression with no significant changes in other validated miRNAs. However, IL-1β-stimulated OA synovial explants exhibited significantly increased expression of miR-23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 186-5p and 378a-5p, and release of only 23a-3p and 27b-3p in supernatants, suggesting that IL-1β contributes to the release of 23a-3p and 27b-3p into the SF from synovium. Computational-analysis identified 2 genes (ROQUIN-1 [RC3H1] and quaking-gene [QKI]) that are targeted by six out of eight miRNAs; miR-27b-3p exhibited greatest association with RC3H1 and QKI genes. Indeed, synovial explants treated with miR-27b-3p-mimic show significant suppression of both RC3H1 and QKI genes., Conclusions: We provide first evidence of the differential expression of circulating miRNAs in early-stage vs late-stage knee OA-SF. Further, we provide source, release and genes/pathways regulated by identified miRNAs., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The majority of patients with hip or knee osteoarthritis (OA) report one or more symptomatic joints apart from the one targeted for surgical care. Therefore, the purpose of the present study was to investigate the association between the burden of multiple symptomatic joints and self-reported depression in patients awaiting joint replacement for OA. Four hundred and seventy-five patients at a single centre were evaluated. Patients self-reported joints that were painful and/or symptomatic most days of the previous month on a homunculus, with nearly one-third of the sample reporting 6 or more painful joints. The prevalence of depression was 12.2% (58/475). When adjusted for age, sex, education level, hip or knee OA, body mass index, chronic condition count, and joint-specific WOMAC scores, each additional symptomatic joint was associated with a 19% increased odds (odds ratio: 1.19 (95% CI: 1.08, 1.31, P < 0.01)) of self-reported depression. Individuals reporting 6 or more painful joints had 2.5-fold or greater odds of depression when compared to those patients whose symptoms were limited to the surgical joint. A focus on the surgical joint alone is likely to miss a potentially important determinant of postsurgical patient-reported outcomes in patients undergoing hip or knee replacement.

Improvements in implant materials and designs have broadened surgical indications and improved the technical successes of joint arthroplasty surgery. Nevertheless, a small but notable proportion of patients remain dissatisfied despite technically successful surgery. Given reported associations between unfulfilled patient expectations and dissatisfaction, we performed a systematic review to investigate the current state of knowledge concerning potential associations between clinical status and patient expectations of joint arthroplasty procedures. A wide range of expectation assessment instruments was identified, some of which assessed probabilistic expectations and other value-based expectations. Consistent associations were identified between probabilistic expectations of surgery and better pre-operative disease-specific and general health status, as well as more desirable post-operative disease specific scores. In contrast, no consistent associations were identified between clinical status and value-based expectations. Fulfillment of expectations was consistently associated with superior disease-specific and general health absolute and change scores, irrespective of the expectations paradigm used.

Background: Avascular necrosis (AVN) of the femoral head (FH) is believed to be caused by a multitude of etiologic factors and is associated with significant morbidity in younger populations. Eventually, the disease progresses and results in FH collapse. Thus, a focus on early disease management aimed at joint preservation by preventing or delaying progression is key. The use of stem cells (SC) for the treatment of AVN of the FH has been proposed. We undertook a systematic review of the medical literature examining the use of SC for the treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and clinical studies., Methods: Data collected included: Pre-clinical studies - model of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical studies - study design, classification and etiology of AVN, SC dosage and treatment protocol, incidence of disease progression, patient reported outcomes, volume of necrotic lesion and hip survivorship., Results: In pre-clinical studies, the use of SC uniformly demonstrated improvements in osteogenesis and angiogenesis, yet source of implanted SC was variable. In clinical studies, groups treated with SC showed significant improvements in patient reported outcomes; however hip survivorship was not affected. Discrepancies regarding dose of SC, AVN etiology and disease severity were present., Conclusions: Routine use of this treatment method will first require further research into dose and quality optimization as well as confirmed improvements in hip survivorship.

Background: Advances in the surgical treatment of musculoskeletal conditions have resulted in an interest in better defining and understanding patients' expectations of these procedures, but the best ways to do this remain a topic of considerable debate., Questions/purposes: (1) What validated instruments for the assessment of patient expectations of orthopaedic surgery have been used in published studies to date? (2) How were these expectation measures developed and validated? (3) What unvalidated instruments for the assessment of patient expectations have been used in published studies to date?, Methods: A systematic literature search was performed using the OVID Medline and EMBASE databases, in duplicate, to identify all studies that assessed patient expectations in orthopaedic surgery. Sixty-six studies were ultimately included in the present review., Results: Seven validated expectation instruments were identified, all of which use patient-reported questionnaires. Five were specific to a particular procedure or affected anatomic location, whereas two were broadly applicable. Details of reliability and validity testing were available for all but one of these instruments. Forty additional unvalidated expectation assessment tools were identified. Thirteen were based on existing clinical outcome tools, and the others were study-specific, custom-developed tools. Only one of the unvalidated tools was used in more than one study., Conclusions: Several validated expectation instruments have been developed for use by patients undergoing orthopaedic surgery. However, many tools have been reported without evidence of testing and validation. The wide range of untested instruments used in single studies substantially limits the interpretation and comparison of data concerning patient expectations.

Objective: To investigate the effect of patient gender on patient-physician communication in the process of recommendation for total knee arthroplasty (TKA)., Methods: Seventy-one physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate knee osteoarthritis and otherwise identical scenarios. Four surgeons did not consent to including their data. Standardized patients and accompanying mock family members recorded elements of informed decision making (IDM) as present/absent in the patient-physician discussion and rated the physicians' interpersonal skills., Results: Overall, the completeness of IDM was low, but was lower still for the woman. Only 57% (38 of 67) and 15% (10 of 67) of physicians discussed the nature of the decision and elicited the patient's preference while consulting with the man and woman, respectively. Even after adjusting for physicians' recommendations regarding TKA, when interacting with the woman, physicians included fewer IDM elements (adjusted mean difference in IDM score 1.2 [95% confidence interval (95% CI) 0.6, 1.8]; P < 0.001) and had poorer interpersonal skills (adjusted mean difference 14.1 [95% CI 9.0, 19.2]; P < 0.001) compared with their consultation with the man., Conclusion: Physicians provided less medical information and less encouragement to participate in the decision to undergo TKA to a woman compared with a man, irrespective of their recommendation regarding TKA. Our findings suggest that in addition to directly influencing physicians' clinical decision making, gender bias may also influence physicians' interpersonal behavior., (Copyright © 2013 by the American College of Rheumatology.)

Objective: Little is known about the relationships among pain, function, psychological variables like perceived helplessness and emotional health, and patient satisfaction in people with revision knee replacement surgery. We hypothesized that pain and function would have a direct association with satisfaction as well as an indirect association through patient perceptions of helplessness and emotional health., Design: This longitudinal study included 145 participants undergoing revision knee replacement surgery. Demographic data and expectation of benefit from surgery were recorded prior to surgery. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Arthritis Helplessness Scale (AHS) and the Mental Component Scale (MCS) of the SF-36 (emotional health) were collected prior to and 2 years post-surgery. Satisfaction was recorded 2 years post-surgery. Regression analyses were conducted to test for mediation effects of helplessness and MCS., Results: Participants were on average 69 years old and 54% were women. Participants were satisfied with the results of the surgery (mean ± standard deviation (SD) = 70.42 ± 31.46). Less pain and functional disability were associated with increased patient satisfaction and, the effect of pain or function was also mediated through helplessness whereby more pain and disability were associated with perceptions of helplessness and helplessness was associated with lower satisfaction. MCS did not mediate the relationship of pain and function with satisfaction., Conclusion: Helplessness plays an important role in understanding patient satisfaction. Interventions aimed at improving patient outcome should target not only pain and function but also should address strategies to support people in managing following knee revision surgery to maximize satisfaction with outcome., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: This population-based cohort study has the objective to understand the sociodemographic characteristics and health conditions of patients who do not receive surgery within 18 months following an ambulatory visit to an orthopaedic surgeon., Methods: Administrative healthcare databases in Ontario, Canada were linked to identify all patients making an initial ambulatory visit to orthopaedic surgeons between October 1(st), 2004 and September 30(th), 2005. Logistic regression was used to examine predictors of not receiving surgery within 18 months., Results: Of the 477,945 patients in the cohort 49% visited orthopaedic surgeons for injury, and 24% for arthritis. Overall, 79.3% did not receive surgery within 18 months of the initial visit, which varied somewhat by diagnosis at first visit (84.5% for injury and 73.0% for arthritis) with highest proportions in the 0-24 and 25-44 age groups. The distribution by income quintile of patients visiting was skewed towards higher incomes. Regression analysis for each diagnostic group showed that younger patients were significantly more likely to be non-surgical than those aged 65+ years (age 0-24: OR 3.45 95%CI 3.33-3.57; age 25-44: OR 1.30 95%CI 1.27-1.33). The odds of not getting surgery were significantly higher for women than men for injury and other conditions; the opposite was true for arthritis and bone conditions., Conclusion: A substantial proportion of referrals were for expert diagnosis or advice on management and treatment. The findings also suggest socioeconomic inequalities in access to orthopaedic care. Further research is needed to investigate whether the high caseload of non-surgical cases affects waiting times to see a surgeon. This paper contributes to the development of evidence-based strategies to streamline access to surgery, and to develop models of care for non-surgical patients to optimize the use of scarce orthopaedic surgeon resources and to enhance the management of musculoskeletal disorders across the care continuum.

Background: The care of injured workers with chronic pain remains an important public health issue given its increasing prevalence. The consequences often include loss of self-esteem and stress in family relationships., Aims: To report our interdisciplinary approach to the care of chronic pain disorder (CPD) and describe the predictors associated with a successful return to work (RTW)., Methods: Relevant covariates, including demographic data, time from injury, and functional scores were recorded for clients injured at work in Ontario, Canada. Our primary outcome, RTW, was assessed at 3 months post-discharge. Descriptive statistics and logistic regression were used to identify those factors predicting a successful RTW., Results: Of the injured workers who participated in the interdisciplinary CPD treatment programme, 1002 clients met our inclusion criteria and were included in the study. Fifty-five per cent were male with a mean age of 46 years. Median time from injury to treatment was 720 days. At 3 months post-treatment, 136 (14%) of the participants were working. Multivariable logistic regression revealed that earlier time since injury (OR = 0.71, 95% CI 0.55-0.92) and presence of an RTW coordinator (RTWC) (OR = 3.42, 95% CI 2.08-5.63) were significant predictors of successful RTW. There was also a significant interaction between RTWC involvement and time since injury. The latter did not appear to influence the likelihood of RTW when an RTWC was present., Conclusions: Workers compensation boards should refer injured workers with CPD to treatment programmes as early as possible to achieve a successful RTW. Additionally, RTWCs play an important role in improving work outcomes.

Background: Tranexamic acid (TXA) is an antifibrinolytic drug used as a blood-sparing technique in many surgical specialties. The principal objective of our meta-analysis was to review randomized, controlled trials (RCT) comparing total blood loss and the number of patients receiving allogeneic blood transfusions with and without the use of TXA for knee (TKA) and hip (THA) arthroplasty., Methods: Studies were included if patients underwent primary unilateral TKA or THA; the study involved the comparison of a TXA treatment group to a control group who received either a placebo or no treatment at all; outcome measures included total blood loss TBL, number of patients receiving allogeneic blood transfusions, and/or incidence of thromboembolic complications; the study was a published or unpublished RCT from 1995 - July 2012., Results: Data were tested for publication bias and statistical heterogeneity. Combined weighted mean differences in blood loss favoured TXA over control for TKA and THA patients respectively [ -1.149 (p < 0.001; 95% CI -1.298, -1.000), -0.504 (p < 0.001; 95% CI, -0.672, -0.336)]. Combined odds ratios favoured fewer patients requiring allogeneic transfusions for TKA and THA with the use of TXA respectively [0.145 (p < 0.001; 95% CI, 0.094, 0.223), 0.327 (p < 0.001; 95% CI, 0.208, 0.515)]. Combined odds ratios indicated no increased incidence of DVT with TXA use in TKA and THA respectively [1.030 (p = 0.946; 95% CI, 0.439, 2.420), 1.070 (p = 0.895; 95% CI, 0.393, 2.911)]., Conclusions: TXA should be considered for routine use in primary knee and hip arthroplasty to decrease blood loss.

Background/aims: Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links., Methods: 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity., Results: 54% of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9) years and the mean BMI (SD) was 28.1 (5.4) kg/m(2). From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p < 0.05). Adipokine levels were not associated with functional outcome scores., Conclusions: The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets., (© 2013 S. Karger GmbH, Freiburg.)

Background: A number of factors have been identified as influencing total knee arthroplasty outcomes, including patient factors such as gender and medical comorbidity, technical factors such as alignment of the prosthesis, and provider factors such as hospital and surgeon procedure volumes. Recently, strategies aimed at optimizing provider factors have been proposed, including regionalization of total joint arthroplasty to higher volume centers, and adoption of volume standards. To contribute to the discussions concerning the optimization of provider factors and proposals to regionalize total knee arthroplasty practices, we undertook a systematic review to investigate the association between surgeon volume and primary total knee arthroplasty outcomes., Methods: We performed a systematic review examining the association between surgeon volume and primary knee arthroplasty outcomes. To be included in the review, the study population had to include patients undergoing primary total knee arthroplasty. Studies had to report on the association between surgeon volume and primary total knee arthroplasty outcomes, including perioperative mortality and morbidity, patient-reported outcomes, or total knee arthroplasty implant survivorship. There were no restrictions placed on study design or language., Results: Studies were variable in defining surgeon volume ('low': <3 to <52 total knee arthroplasty per year; 'high': >5 to >70 total knee arthroplasty per year). Mortality rate, survivorship and thromboembolic events were not found to be associated with surgeon volume. We found a significant association between low surgeon volume and higher rate of infection (0.26% - 2.8% higher), procedure time (165 min versus 135 min), longer length of stay (0.4 - 2.13 days longer), transfusion rate (13% versus 4%), and worse patient reported outcomes., Conclusions: Findings suggest a trend towards better outcomes for higher volume surgeons, but results must be interpreted with caution.

Background: Specially trained physiotherapists (advanced practice physiotherapists (APP)) are working in orthopaedic clinics to improve access to orthopaedic services and support chronic disease management. Little attention has been paid to the impact APPs may have on non-surgical patients. In non-surgical patients with hip or knee arthritis consulting an APP in an orthopaedic clinic, the objectives were to: 1) describe patients' recall of APP recommendations, use of self-management strategies, and barriers to management six weeks following consultation; and, 2) compare exercise behaviour and self-efficacy at baseline and six weeks., Findings: This was a single group pre-and post-intervention study of patients who saw an APP when consulting the orthopaedic departments of two hospitals. At baseline and six weeks participants completed the adapted Stanford Exercise Behaviour Scale (response options: none, < 60 minutes/week, 1-3 hours/week or > 3 hours/week), and the Chronic Disease Self-efficacy Scale (range 1-10; higher scores indicate higher self-efficacy). At follow-up participants completed questions on recall of APP recommendations, use of self-management strategies and barriers to management. Seventy three non-surgical patients with hip or knee arthritis participated, a response rate of 89% at follow-up. Seventy one percent of patients reported that the APP recommended exercise, of whom 83% reported exercising to manage their arthritis since the visit. Almost 50% reported an increase in time spent stretching; over 40% reported an increase in time spent walking or doing strengthening exercises at follow-up. Common barriers to arthritis management were time, cost and other health problems. Mean chronic disease self-efficacy scores significantly improved from 6.3 to 7.2 (p < 0.001). The mean difference was 0.95 (95% CI 0.43, 1.62); the effect size was 0.51., Conclusions: This pilot study of an APP intervention for non-surgical patients referred for orthopaedic consultation showed promising results, particularly for enhancing use of conservative management strategies such as exercise.

Objective: To determine whether symptomatic (painful/problematic) joints pre-total knee replacement (TKR) surgery influence 1) pre- and 12-month post-TKR patient-reported outcomes (pain, physical function, and mood [fatigue, anxiety, and depression]) and 2) postsurgical pain and function mediated through mood., Methods: A total of 494 participants completed the patient-reported outcome measures pre- and 12-months post-TKR. Symptomatic (painful/problematic) joints affected by arthritis were indicated on a homunculus presurgery. Covariate data included age, sex, educational attainment, body mass index, and comorbidity. Pre- and postsurgical outcome scores were regressed on symptomatic joint sites and covariates using linear regression analyses; postsurgical scores additionally were regressed on presurgery scores. Path analyses examined whether the effects of symptomatic joint sites on postsurgical pain and function were mediated through mood., Results: The age range was 35-88 years (mean 65 years) and 65% were women. Forty-six percent reported ≥4 symptomatic joints (other than the surgical knee). Pre- and postsurgery, worse outcome scores were observed with increasing joint count. Adjusted for covariates, individuals reporting symptomatic ankles/feet/toes, neck, and spine/lower back had worse presurgery fatigue and anxiety. Adjusted for covariates and presurgery status, worse fatigue for the neck and spine/lower back and worse depression, pain, and function for the ankles/feet/toes and neck were observed postsurgery. The influence of symptomatic ankles/feet/toes on postsurgical pain and function was in part direct and partially mediated through depression. Full mediation was found for the neck through fatigue, anxiety, and depression, and for the spine/lower back through fatigue., Conclusion: Findings suggest that a comprehensive approach to osteoarthritis management/care is warranted, and identify important associations between symptomatic joints and mood that negatively impact post-TKR pain and physical function., (Copyright © 2012 by the American College of Rheumatology.)

Background: After the Food and Drug Administration Modernization Act of 1997, the registration of all clinical trials became mandatory prior to publication. Our primary objective was to determine publication rates for orthopaedic trauma trials registered with ClinicalTrials.gov. We further evaluated methodological consistency between registration and publication., Methods: We searched Clinical Trials.gov for all trials related to orthopaedic trauma. We excluded active trials and trials not completed by July 2009, and performed a systematic search for publications resulting from registered closed trials. Information regarding primary and secondary outcomes, intervention, study sponsors, and sample size were extracted from registrations and publications., Results: Of 130 closed trials, 37 eligible trials resulted in 16 publications (43.2%). We found no significant differences in publication rates between funding sources for industry sponsored studies and nongovernment/nonindustry sponsored studies (p > 0.05). About half the trials (45%) did not include the NCT ID in the publication. Two (10%) publications had major changes to the primary outcome measure and ten (52.6%) to sample size., Conclusions: Registration of orthopaedic trauma trials does not consistently result in publication. When trials are registered, many do not cite NCT ID in the publication. Furthermore, changes that are not reflected in the registry of the trial are frequently made to the final publication.

Objective: Primary total hip (THR) and knee (TKR) replacement outcomes typically include pain and function with a single time of follow-up post-surgery. This research evaluated the trajectory of recovery and inter-relationships within and across time of physical impairments (PI) (e.g., symptoms), activity limitations (AL), and social participation restrictions (PR) in the year following THR and TKR for osteoarthritis., Design: Participants (hip: n=437; knee: 494) completed measures pre-surgery and at 2 weeks, 1, 3, 6 and 12 months post-surgery. These included PI (Hip Disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and Chronic Pain Grade); AL (HOOS/KOOS activities of daily living and sports/leisure activities); and, PR (Late Life Disability and the Calderdale community mobility). Repeated measures analysis of variance (RANOVA) was used to evaluate the trajectory of recovery of outcomes and the inter-relationships of PI, AL and PR were evaluated using path analysis. All analyses were adjusted for age, sex, obesity, THR/TKR, low back pain and mood., Results: THR: age 31-86 years with 55% female; TKR: age 35-88 years with 65% female. Significant improvements in outcomes were observed over time. However, improvements were lagged over time with earlier improvements in PI and AL and later improvements in PR. Within and across time, PI was associated with AL and AL was associated with PR. The magnitude of these inter-relationships varied over time., Conclusion: Given the lagged inter-relationship of PI, AL and PR, the provision and timing of interventions targeting all constructs are critical to maximizing outcome. Current care pathways focusing on short-term follow-up with limited attention to social and community participation should be re-evaluated., (Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the pain and functional disability levels corresponding to an indication for total joint replacement (TJR) in hip and knee osteoarthritis (OA)., Design: International cross-sectional study in 10 countries., Patients: Consecutive outpatients with definite hip or knee OA attending an orthopaedic outpatient clinic. Gold standard measure for recommendation for TJR: Surgeon's decision that TJR is justified., Outcome Measures: Pain (ICOAP: intermittent and constant osteoarthritis pain, 0-100) and functional impairment (HOOS-PS/KOOS-PS: Hip/Knee injury and Osteoarthritis Outcome Score Physical function Short-form, 0-100)., Analyses: Comparison of patients with vs without surgeons' indication for TJR. Receiver Operating Characteristic (ROC) curve analyses and logistic regression were applied to determine cut points of pain and disability defining recommendation for TJR., Results: In all, 1909 patients were included (1130 knee/779 hip OA). Mean age was 66.4 [standard deviation (SD) 10.9] years, 58.1% were women; 628/1130 (55.6%) knee OA and 574/779 (73.7%) hip OA patients were recommended for TJR. Although patients recommended for TJR (yes vs no) had worse symptom levels [pain, 55.5 (95% confidence interval 54.2, 56.8) vs. 44.9 (43.2, 46.6), and functional impairment, 59.8 (58.7, 60.9) vs. 50.9 (49.3, 52.4), respectively, both P<0.0001], there was substantial overlap in symptom levels between groups, even when adjusting for radiographic joint status. Thus, it was not possible to determine cut points for pain and function defining 'requirement for TJR'., Conclusion: Although symptom levels were higher in patients recommended for TJR, pain and functional disability alone did not discriminate between those who were and were not considered to need TJR by the orthopaedic surgeon., (Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Obesity has been identified as a risk factor for the development of hip and knee osteoarthritis (OA) and may play a role in exacerbating existing disease. Therefore, we hypothesized that obese patients would present for hip and knee replacement surgery at a younger age than nonobese patients. From our registry, we performed a cross-sectional study of 841 hip and 804 knee replacement patients. Patients were categorized by BMI ≤ 25 kg/m(2), 25.1-29.9 kg/m(2), 30-34.9 kg/m(2), and ≥ 35 kg/m(2). Linear regression modeling was used to examine the relationship between BMI and age at surgery. Hip and knee replacement patients' mean age at surgery was 7.1 and 7.9 years younger, respectively, if their BMI was ≥ 35 kg/m(2) when compared to patients with a BMI ≤ 25 kg/m(2) (P = 0.002). BMI was a significant independent (of gender, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, surgeon, and comorbidity) predictor of age at knee replacement (P < 0.05). WOMAC scores were significantly worse preoperatively in patients with a BMI ≥ 35 kg/m(2) compared to those with a BMI ≤ 25 kg/m(2) (P < 0.05). Our study indicates that obese patients, especially those with a BMI ≥ 35 kg/m(2), presented for and underwent joint replacement surgery at a younger age as compared to nonobese patients.

Background: Studies on critical pathway use have demonstrated decreased length of stay and cost without compromise in quality of care. However, pathway effectiveness is difficult to determine given methodological flaws, such as small or single center cohorts. We studied the effect of critical pathways on total knee replacement outcomes in a large population-based study., Methods: We identified hospitals in four US states that performed total knee replacements. We sent a questionnaire to surgical administrators in these hospitals including items about critical pathway use and hospital characteristics potentially related to outcomes. Patient data were obtained from Medicare claims, including demographics, comorbidities, 90-day postoperative complications and length of hospital stay. The principal outcome measure was the risk of having one or more postoperative complications., Results: Two hundred ninety five hospitals (73%) responded to the questionnaire, with 201 reporting the use of critical pathways. 9,157 Medicare beneficiaries underwent TKR in these hospitals with a mean age of 74 years (+/- 5.8). After adjusting for both patient and hospital related variables, patients in hospitals with pathways were 32% less likely to have a postoperative complication compared to patients in hospitals without pathways (OR 0.68, 95% CI 0.50-0.92). Patients managed on a critical pathway had an average length of stay 0.5 days (95% CI 0.3-0.6) shorter than patients not managed on a pathway., Conclusion: Medicare patients undergoing total knee replacement surgery in hospitals that used critical pathways had fewer postoperative complications than patients in hospitals without pathways, even after adjusting for patient and hospital related factors. This study has helped to establish that critical pathway use is associated with lower rates of postoperative mortality and complications following total knee replacement after adjusting for measured variables.

Purpose: The present study investigated whether the conceptualization of hip and knee osteoarthritis pain implicit in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Medical Outcomes Study Short-Form 36 (SF-36) scales is complete, or whether the addition of another scale, such as the Short-Form McGill Pain Questionnaire (MPQ-SF), provides a more complete characterization. Furthermore, the impact that mental health symptoms and catastrophizing had on these scales was investigated., Methods: Before hip and knee arthroplasty, 200 patients completed surveys of demographic data, the WOMAC pain scale, the MPQ-SF, the SF-36 Bodily Pain scale, the Pain Catastrophizing Scale and the Hospital Anxiety and Depression Scale. Correlations between scales were calculated and linear regression modelling was used to determine the impact of mental health and catastrophizing on these three pain measures., Results: A strong correlation between the WOMAC and SF-36 pain scales (r=-0.70) was found; however, both correlated only moderately with the MPQ-SF (r=0.36 and r=-0.36, respectively). Linear regression modelling showed that the Pain Catastrophizing Scale significantly predicted a greater score on all three pain scales (P<0.05)., Conclusions: The addition of the MPQ-SF appears to add to a more complete quantification of the pain experience in hip and knee osteoarthritis.

Background: Studies have shown that women present for surgery at an older age and with greater dysfunction than do men; however, the explanation for this finding is unclear. We investigated the impact living status (alone or with another person) and sex on the timing and outcomes of hip and knee replacement surgery., Methods: We surveyed 1722 patients undergoing primary hip or knee replacement surgery. Relevant covariates including demographic data, body mass index, sex, living status and comorbidities were recorded. We assessed joint pain and functional status before surgery and at 3 months and 1 year after surgery using the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores for pain and function., Results: In total, 22.9% (395) of all patients (29.3% of women and 14.1% of men) were living alone at the time of surgery. Compared with patients who lived with another person, those who lived alone were significantly older, had greater comorbidity and reported greater joint pain and dysfunction before surgery and 3 months and 1 year after surgery. Living alone and female sex independently predicted a greater preoperative WOMAC score, and living alone predicted an older age at the time of surgery and a poorer 1-year outcome., Conclusion: Patients who live alone may delay joint replacement surgery until an older age and have greater joint pain and dysfunction than those who live with another person, leading to poorer 1-year outcomes.

Unlabelled: Despite substantial advances in primary TKA, numerous studies using historic TKA implants suggest only 82% to 89% of primary TKA patients are satisfied. We reexamined this issue to determine if contemporary TKA implants might be associated with improved patient satisfaction. We performed a cross-sectional study of patient satisfaction after 1703 primary TKAs performed in the province of Ontario. Our data confirmed that approximately one in five (19%) primary TKA patients were not satisfied with the outcome. Satisfaction with pain relief varied from 72-86% and with function from 70-84% for specific activities of daily living. The strongest predictors of patient dissatisfaction after primary TKA were expectations not met (10.7x greater risk), a low 1-year WOMAC (2.5x greater risk), preoperative pain at rest (2.4x greater risk) and a postoperative complication requiring hospital readmission (1.9x greater risk)., Level of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.