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Rajiv Gandhi,1,2 Anthony V Perruccio,1,3 Y Raja Rampersaud1,21Division of Orthopaedic Surgery, Toronto Western Hospital, University Health Network, 2Department of Surgery, Faculty of Medicine, University of Toronto, 3Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, CanadaPurpose: Knowledge of what influences patients’ willingness to undergo elective orthopedic surgery is vital to the patient shared decision-making process. We sought to document the prevalence and identify the predictors of unwillingness to undergo surgery among a cohort of hip/knee, foot/ankle, neck/back, and hip/knee patients.Patients and methods: Patient demographics and information on patient health status, perceptions of risk and success of surgery, and willingness to undergo surgery were collected. Sequential logistic regression models were used to investigate the influence of the captured variables on willingness to undergo surgery.Results: Overall, 392 (20%) of 1946 participants reported being unwilling to undergo or unsure about undergoing (“unwilling/unsure”) surgery if it was offered to them. From adjusted analyses, low income and non-White ethnicity were associated with a greater likelihood of being unwilling/unsure. Compared with hip/knee patients, neck/back patients were more likely to report being unwilling/unsure (odds ratio: 1.90 [95% confidence interval: 1.36, 265]); no differences were found between the remaining anatomical groups. However, when perceptions of risk and success were additionally considered, the influence for the neck/back cohort was significantly attenuated. Foot/ankle and elbow/shoulder patients were found to be significantly less likely to report unwillingness when perceptions were considered.Conclusion: In addition to demographic/economic influences, perceptions of surgical risk and success play a critical role in patients’ willingness to undergo surgery.Keywords: risk perception, orthopedic surgery, patient perceptions, ethnicity

Objective: The purpose of the study is to examine the relationship between osteoarthritis (OA) and joint symptoms typical of OA and labor force participation., Methods: Data are from the baseline questionnaire of the Canadian Longitudinal Study on Aging for respondents aged 45 to 74 years at baseline (n = 24,427). Individuals were categorized into one of five mutually exclusive arthritis status groups: diagnosed OA, diagnosed other type of arthritis, two to three symptomatic joint sites and no diagnosed arthritis, one symptomatic joint site and no diagnosed arthritis, and no arthritis and no joint symptoms. Age-stratified robust log-Poisson regression analysis was used to examine the association between arthritis status and labor force participation., Results: Overall, 39% of the analytic sample reported being out of the labor force. Those with OA aged 45 to 54 and 55 to 64 years were significantly more likely to be out of the labor force than those with no arthritis or no joint symptoms, with prevalence ratios (PRs) of 1.34 (95% confidence interval [CI] 1.10-1.65) and 1.13 (95% CI 1.06-1.21), respectively, with similar results for those with two to three joint symptoms and no OA in the 45 to 54 years age group (PR 1.37 [95% CI 1.07-1.76]). There was no difference for those aged 65 to 74 years. Being an informal caregiver increased the likelihood of nonparticipation in the labor force for those aged 55 to 64 years (PR 1.09 [95% CI 1.04-1.15])., Conclusion: Our results suggest that an exclusive reliance on an OA diagnosis to understand impact on labor force participation may miss a large segment of the middle-aged population, which may have undiagnosed OA or be at greater risk of OA because of joint problems., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: In this study, we employ a multiomic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex and obesity status., Methods: Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analyses were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature. The diversity of fibroblasts within the IFP was investigated by bioinformatic analyses, comparing by KOA, sex and obesity status. Metabolomics was used to further explore differences in fibroblasts by obesity status., Results: We identified multiple subclusters of fibroblasts, macrophages, adipocytes and endothelial cells with unique transcriptomic profiles. Using spatial transcriptomics, we resolved distributions of cell types and their transcriptomic profiles and computationally identified putative cell-cell communication networks. Furthermore, we identified transcriptomic differences in fibroblasts from KOA versus healthy control donor IFPs, female versus male KOA-IFPs and obese versus normal body mass index (BMI) KOA-IFPs. Finally, using metabolomics, we defined differences in metabolite levels in supernatants of naïve, profibrotic stimuli-treated and proinflammatory stimuli-treated fibroblasts from obese compared to normal BMI KOA-IFPs., Conclusions: Overall, by employing a multiomic approach, this study provides the first comprehensive map of the cellular and transcriptomic diversity of human IFP and identifies IFP fibroblasts as key cells contributing to transcriptomic and metabolic differences related to KOA disease, sex or obesity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: Osteoarthritis (OA) is frequently perceived as a disease of the elderly and an inevitable result of aging. Because OA studies often are restricted to older adults, there is limited information on OA in younger adults. This study describes the burden of OA across a wide age range and compares younger and older adults., Methods: Descriptive analysis of the Survey on Living with Chronic Diseases in Canada - Arthritis Component, a nationally representative survey of Canadians ≥20 years who reported an arthritis diagnosis in the Canadian Community Health Survey, a general health population survey. Analyses were restricted to those reporting OA and no other kind of arthritis (n = 1,749)., Results: In the representative group with OA, 55.4% were younger than 65 years. The mean age at diagnosis was 50 years, with 30.4% reporting being diagnosed before age 45 years. Younger adults reported similar symptom severity as their older counterparts with OA regarding the mean number of affected joint sites, severity of pain and fatigue, and activity limitations. In the youngest age group, those with OA were significantly more likely to report fair or poor overall and mental health and life dissatisfaction compared with their general counterparts; the same was not the case in the oldest age group., Conclusion: OA is not uncommon among younger and middle-aged adults, and they experience OA impacts comparable with those for older adults. These findings suggest that younger adults with OA will live many years with symptoms and disability and highlight a need for effective OA management across ages., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu + Ex) programs may reduce the number of THAs needed, but supporting data are limited. This study aimed to estimate the treatment effect of THA versus Edu + Ex on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for hip OA., Methods: Patients who had hip OA who underwent THA or an Edu + Ex program were included in this propensity-matched study. In 778 patients (Edu + Ex, n = 303; THA, n = 475), propensity scores were based on pretreatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference (MD) in change from pretreatment to 3-month and 12-month follow-up using linear mixed models., Results: The matched sample consisted of 266 patients (Edu + Ex, n = 133; THA, n = 133) who were balanced on all pretreatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (MD 35.4; 95% confidence interval [CI] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17% and 30% of patients receiving Edu + Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84% and 90% of THA patients., Conclusions: A THA provides greater improvements in pain, function, and quality of life. A notable proportion of Edu + Ex patients had clinically meaningful improvements, suggesting Edu + Ex may result in THA deferral in some patients, but confirmatory trials are needed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Age and sex differences may exist in the frequency (incidence, prevalence) or symptoms of neuropathic pain (NP) and complex regional pain syndrome (CRPS) due to biopsychosocial factors (eg, neurodevelopment, physiological and hormonal changes, psychosocial differences) that evolve through childhood and adolescence. Age and sex differences may have implications for evaluating screening and diagnostic tools and treatment interventions., Objective: To map the existing literature on pediatric NP and CRPS with respect to age and sex distributions, and age and sex differences in symptomology and frequency., Methods: A scoping literature review was conducted. Databases were searched from inception to January 2023. Data were collected on study design, setting, demographics, and age and sex differences in frequency and symptoms., Results: Eighty-seven studies were included. Distribution of participants with CRPS (n=37 studies) was predominantly early adolescence (10 to 14 y) and female sex, while NP (n=42 studies) was most commonly reported throughout adolescence (10 to 19 y) in both sexes. Forty-one studies examined age and sex differences in frequency; 6 studies reported higher frequency in adolescence. Very few studies (n=11) examined differences in symptomology., Discussion: Large epidemiological studies are required to further understand age and sex differences in frequency of pediatric NP and CRPS. Age and sex differences must be considered when evaluating screening and diagnostic tools and treatment interventions to ensure relevance and validity to both sexes and across ages. Validated tools will improve understanding of age-dependent and sex-dependent differences in symptoms, pathophysiology, and psychosocial impact of pediatric NP and CRPS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 characterization and influence of preoperative health care use on quality-of-care indicators (e.g., readmissions) has received limited attention in populations with musculoskeletal disorders. The purpose of this study was to characterize preoperative health care use and examine its effect on quality-of-care indicators among patients undergoing elective surgery for osteoarthritis., Methods: Data on health care use for 124,750 patients with elective surgery for osteoarthritis in Ontario, Canada, from April 1, 2015 to March 31, 2018 were linked across health administrative databases. Using total health care use one-year previous to surgery, patients were grouped from low to very high users. We used Poisson regression models to estimate rate ratios, while examining the relationship between preoperative health care use and quality-of-care indicators (e.g., extended length of stay, complications, and 90-day hospital readmissions). We controlled for covariates (age, sex, neighborhood income, rural/urban residence, comorbidities, and surgical anatomical site)., Results: We found a statistically significant trend of increasing worse outcomes by health care use gradients that persisted after controlling for patient demographics and comorbidities. Findings were consistent across surgical anatomical sites. Moreover, very high users have relatively large numbers of visits to non-musculoskeletal specialists., Conclusions: Our findings highlight that information on patients' preoperative health care use, together with other risk factors (such as comorbidities), could help decision-making when benchmarking or reimbursing hospitals caring for complex patients undergoing surgery for osteoarthritis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: In osteoarthritis (OA) research, disability is largely studied within the context of activities of daily living. Broader consequences for social participation are often overlooked. In prior work, instrumental supports received and their perceived availability were shown to play a role in the maintenance of social participation. Two indicators of social participation were identified, diversity and intensity. The current study extends the findings from this prior cross-sectional work by examining these relationships longitudinally., Methods: Data are from the baseline and 3-year follow-up questionnaires of the Canadian Longitudinal Study on Aging, a population-based study of people ages 45-85 years at baseline. The sample was restricted to those who at baseline reported a doctor diagnosis of OA (n = 4104). Using structural equation modeling, latent variables were derived at each time point for activity limitations, instrumental supports perceived and received, and social participation diversity and intensity. Longitudinal factorial invariance was assessed. Model covariates included age, sex, education, income, marital status, smoking status, obesity, and number of chronic conditions., Results: For all latent variables, strong factorial longitudinal invariance was found. Activity limitations increased over time. Greater baseline social participation intensity was associated with increases in later intensity and diversity. Increasing activity limitations were associated with decreases in social participation and with increasing receipt of instrumental supports; they were not associated with changes in perceived availability of supports. However, increasing perceived availability was positively associated with social participation intensity., Conclusions: With a goal of increasing social participation, findings suggest a focus on interventions to reduce activity limitations in OA is necessary. Findings additionally highlight an important role for perceived availability of instrumental supports in maintaining or improving social participation in OA, in addition to current social participation, particularly intensity, for future social participation status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Perruccio 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.)

Objective: To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year., Methods: Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches., Results: 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors - population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences., Conclusions: Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes., Methods: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models., Results: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not., Conclusions: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest related to this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Increased use of opioids and their associated harms have raised concerns around prescription opioid use for pain management following surgery. We examined trends and patterns of opioid prescribing following elective orthopaedic surgery., Design: Population-based study., Setting: Ontario, Canada., Participants: Ontario residents aged 66+ years who had elective orthopaedic surgery from April 2004 to March 2018., Primary and Secondary Outcome Measures: Postoperative opioid use (short term: within 90 days of surgery, prolonged: within 180 days and chronic: within 1 year), specific opioids prescribed, average duration (days) and amount (morphine milligram equivalents) of the initial prescription by year of surgery., Results: We included 464 460 elective orthopaedic surgeries in 2004/2005-2017/2018: 80% of patients used opioids within 1 year of surgery-25.1% were chronic users. There was an 8% increase in opioid use within 1 year of surgery, from 75.1% in 2004/2005 to 80.9% in 2017/2018: a 29% increase in short-term use and a decline in prolonged (9%) and chronic (22%) use. After 2014/2015, prescribed opioid amounts initially declined sharply, while the duration of the initial prescription increased substantially. Across categories of use, there was a steady decline in coprescription of benzodiazepines and opioids., Conclusions: Most patients filled opioid prescriptions after surgery, and many continued filling prescriptions after 3 months. During a period of general increase in awareness of opioid harms and dissemination of guidelines/policies aimed at opioid prescribing for chronic pain, we found changes in prescribing practices following elective orthopaedic surgery. Findings illustrate the potential impact of guidelines/policies on shaping prescription patterns in the surgical population, even in the absence of specific guidelines for surgical prescribing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To characterize the profile of individuals with and without knee osteoarthritis (OA) who fell, and to identify factors contributing to an individual with knee OA experiencing 1 or multiple injurious falls., Methods: Data are from the baseline and 3-year follow-up questionnaires of the Canadian Longitudinal Study on Aging, a population-based study of people ages 45-85 years at baseline. Analyses were limited to individuals either reporting knee OA or no arthritis at baseline (n = 21,710). Differences between falling patterns among those with and without knee OA were tested using chi-square tests and multivariable-adjusted logistic regression models. An ordinal logistic regression model examined predictors of experiencing 1 or more injurious falls among individuals with knee OA., Results: Among individuals reporting knee OA, 10% reported 1 or more injurious falls; 6% reported 1 fall, and 4% reported 2+ falls. Having knee OA significantly contributed to the risk of falling (odds ratio [OR] 1.33 [95% confidence interval (95% CI) 1.14-1.56]), and individuals with knee OA were more likely to report having a fall indoors while standing or walking. Among individuals with knee OA, reporting a previous fall (OR 1.75 [95% CI 1.22-2.52]), previous fracture (OR 1.42 [95% CI 1.12-1.80]), and having urinary incontinence (OR 1.38 [95% CI 1.01-1.88]) were significant predictors of falling., Conclusion: Our findings support the idea that knee OA is an independent risk factor for falls. The circumstances in which falls occur differ from those for individuals without knee OA. The risk factors and environments that are associated with falling may provide opportunities for clinical intervention and fall prevention strategies., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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.)

Background Context: There is significant variability in minimal clinically important difference (MCID) criteria for lumbar spine surgery that suggests population and primary pathology specific thresholds may be required to help determine surgical success when using patient reported outcome measures (PROMs)., Purpose: The purpose of this study was to estimate MCID thresholds for 3 commonly used PROMs after surgical intervention for each of 4 common lumbar spine pathologies., Study Design/setting: Observational longitudinal study of patients from the Canadian Spine Outcomes and Research Network (CSORN) national registry., Patient Sample: Patients undergoing surgery from 2015 to 2018 for lumbar spinal stenosis (LSS; n = 856), degenerative spondylolisthesis (DS; n = 591), disc herniation (DH; n = 520) or degenerative disc disease (DDD n = 185) were included., Outcome Measures: PROMs were collected presurgery and 1-year postsurgery: the Oswestry Disability Index (ODI), and back and leg Numeric Pain Rating Scales (NPRS). At 1-year, patients reported whether they were 'Much better'/'Better'/'Same'/'Worse'/'Much worse' compared to before their surgery. Responses to this item were used as the anchor in analyses to determine surgical MCIDs for benefit ('Much better'/'Better') and substantial benefit ('Much better')., Methods: MCIDs for absolute and percentage change for each of the 3 PROMs were estimated using a receiving operating curve (ROC) approach, with maximization of Youden's index as primary criterion. Area under the curve (AUC) estimates, sensitivity, specificity and correct classification rates were determined. All analyses were conducted separately by pathology group., Results: MCIDs for ODI change ranged from -10.0 (DDD) to -16.9 (DH) for benefit, and -13.8 (LSS) to -22.0 (DS,DH) for substantial benefit. MCID for back and leg NPRS change were -2 to -3 for each group for benefit and -4.0 for substantial benefit for all groups on back NPRS. MCID estimates for percentage change varied by PROM and pathology group, ranging from -11.1% (ODI for DDD) to -50.0% (leg NPRS for DH) for benefit and from -40.0% (ODI for DDD) to -66.6% (leg NPRS for DH) for substantial benefit. Correct classification rates for all MCID thresholds ranged from 71% to 89% and were relatively lower for absolute vs percent change for those with high or low presurgical scores., Conclusions: Our findings suggest that the use of generic MCID thresholds across pathologies in lumbar spine surgery is not recommended. For patients with relatively low or high presurgery PROM scores, MCIDs based on percentage change, rather than absolute change, appear generally preferable. These findings have applicability in clinical and research settings, and are important for future surgical prognostic work., Competing Interests: Declarations of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: In OA studies, the focus often is on an index-joint; other affected joint sites are often overlooked. In this thumb-base OA study, we documented the frequency of symptomatic non-hand joint sites and investigated whether their count was associated with thumb-specific functional and patient-reported outcome measures., Design: Patients seeking care for thumb-base OA (conservative or surgical) were included. A patient-completed questionnaire captured sociodemographic and health characteristics, symptomatic hand and non-hand joint sites, and outcome measures (thumb-base pain intensity, symptoms and disability (TASD) and upper-extremity disability/symptoms (quickDASH)). Grip and pinch strength were measured. Linear regressions examined the association between each outcome and symptomatic joint site count, adjusted for several covariates., Results: The mean age of the 145 patients was 62 years, 72% were female. Mean symptomatic non-hand joint site count was 3.6. Ten percent reported only their hands as symptomatic; 30% reported 2-3 other symptomatic sites, and 49% reported 4+. From cross-sectional multivariable analyses, a higher symptomatic non-hand joint site count was associated with worse scores for all patient-reported outcomes and grip strength. Every unit increase in joint site count (49% had a 4+ count) was associated with a 2.1-3.3 unit increase (worse) in patient-reported outcome scores (all p ​< ​0.02)., Conclusions: In this sample, nearly 80% of patients had 2+ symptomatic non-hand joint sites. These symptoms were associated with worse thumb- and hand-specific outcomes, suggesting a need for awareness of whole body OA burden, with implications for outcome score interpretations, study designs, and provision of care in thumb-base OA., Competing Interests: AVP: none. EMB: none. DA: none. JDP: none. HB: none., (© 2023 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI).)

Background: The Good Life with osteoArthritis in Denmark (GLA:D®) program was implemented in Canada in 2017 with the aim of making treatment guideline-recommended care available to the 4 million Canadians with knee and hip osteoarthritis (OA). This report describes the GLA:D® Canada program, registry and data collection procedures, and summarizes the sociodemographic and clinical profile of participants with knee and hip OA to inform the scientific research community of the availability of these data for future investigations and collaborations., Methods: The GLA:D® program consists of three standardized components: a training course for health care providers, a group-based patient education and exercise therapy program, and a participant data registry. Patients seeking care for knee or hip OA symptoms and enrolling in GLA:D® are given the option to provide data to the GLA:D® Canada registry. Participants agreeing to provide data complete a pre-program survey and are followed up after 3-, and 12-months. Data collected on the pre-program and follow-up surveys include sociodemographic factors, clinical characteristics, health status measures, and objective physical function tests. These variables were selected to capture information across relevant health constructs and for future research investigations., Results: At 2022 year-end, a total of 15,193 (11,228 knee; 3,965 hip) participants were included in the GLA:D® Canada registry with 7,527 (knee; 67.0%) and 2,798 (hip; 70.6%) providing pre-program data. Participants were 66 years of age on average, predominately female, and overweight or obese. Typically, participants had knee or hip problems for multiple years prior to initiating GLA:D®, multiple symptomatic knee and hip joints, and at least one medical comorbidity. Before starting the program, the average pain intensity was 5 out of 10, with approximately 2 out of 3 participants using pain medication and 1 in 3 participants reporting a desire to have joint surgery. Likewise, 9 out 10 participants report having previously been given a diagnosis of OA, with 9 out 10 also reporting having had a radiograph, of which approximately 87% reported the radiograph showed signs of OA., Conclusion: We have described the GLA:D® Canada program, registry and data collection procedures, and provided a detailed summary to date of the profiles of participants with knee and hip OA. These individual participant data have the potential to be linked with local health administrative data registries and comparatively assessed with other international GLA:D® registries. Researchers are invited to make use of these rich datasets and participate in collaborative endeavours to tackle questions of Canadian and global importance for a large and growing clinical population of individuals with hip and knee OA., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JJY is the Assistant Project Manager for the GLA:D® International Network. AVP has no competing interested to declare. CJHV has served as a paid consultant, editorial board member, or governing board member, or received research support from Zimmer Biomet, CODMAN Group, DePuy Synthes, Orthogate, Orthopaedic Web Links, OrthopaedicsOne, and Smith and Nephew. RAM is the National Director of GLA:D® Canada and Executive Director of Bone and Joint Canada. MGZ is the Primary Investigator for the GLA:D® Canada registry and has served as a paid consultant to the following: Smith and Nephew, DePuy Synthes, Johnson & Johnson, and OPEXC Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Young 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.)

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.)

Objective: To understand factors associated with pain intensity responder status following nonsurgical hip osteoarthritis (OA) intervention, according to sex., Methods: Data were from individuals with hip OA participating in the Danish Good Life With Osteoarthritis in Denmark 8-week education and exercise program. The following factors were recorded at program entry: age; education; mental well-being; comorbidities; body mass index; symptoms in hip, knee, and low back; and program-specific factors including education sessions, former participant lectures, and supervised exercise sessions. Pain intensity was recorded at baseline and at month 3 (post-program) on a 0-100-mm visual analog scale. Response was defined as pain intensity improvement of ≥30% from baseline to post-program. Logistic regression was used and conducted separately in male and female subjects., Results: The sample included 791 men and 2,253 women. Female subjects had a mean baseline pain score of 47.2 of 100 (95% confidence interval [95% CI] 46.4-48.1) and male subjects had a score of 41.7 (95% CI 40.3-43.1). By post-program, the proportion of pain responders was 50.4% among women and 45.8% among men (difference P = 0.025). Among women, program-specific factors (attending former participant lectures and more supervised exercise sessions) were positively associated with pain response, as were better mental well-being and fewer comorbidities, while symptoms in other joints/sites were associated with a decreased likelihood of response. Among men, program-specific factors were not associated with response, while better mental well-being and fewer comorbidities were associated with being a responder., Conclusion: Findings suggest that the influence of some factors on pain response differ for male and female subjects and point to a potential need for targeted approaches for men and women who may require different key messages/approaches from health care providers., (© 2022 American College of Rheumatology.)

Objective: The objective of this study was to investigate a profile of cardiovascular disease (CVD) risk factors by sex among individuals with and without osteoarthritis (OA) and to consider single-site and multisite joint OA., Methods: Data were sourced from Cycle 1, Comprehensive Cohort, Canadian Longitudinal Study on Aging, a national sample of individuals ages 45 to 85 years. Systemic inflammatory/metabolic CVD risk factors collected were high-sensitivity C-reactive protein (hsCRP) level, high-density lipoprotein, triglycerides, total cholesterol, body mass index (BMI), systolic blood pressure, and hemoglobin A1c. Smoking history was also collected. Respondents indicated doctor-diagnosed OA in the knees, hips, and/or hands and were characterized as yes/no OA and single site/multisite OA. Individuals with OA were age- and sex-matched to non-OA controls. Covariates were age, sex, education, income, physical activity, timed up and go test findings, and comorbidities. A latent CVD risk variable was derived in women and men; standardized scores were categorized as follows: lowest, mid-low, mid-high, and highest risk. Associations with OA were quantified using ordinal logistic regressions., Results: A total of 6,098 respondents (3,049 with OA) had a median age of 63 years, and 55.8% were women. One-third of OA respondents were in the highest risk category versus one-fifth of non-OA respondents. Apart from BMI (the largest contributor in both sexes), hsCRP level (an inflammation marker) was predominant in women, and metabolic factors and smoking were predominant in men. Overall, OA was associated with worse CVD risk quartiles compared with non-OA. OA was increasingly associated with worse CVD risk quartiles with increasing risk thresholds among women with multisite OA, but not men., Conclusion: Findings suggest unique CVD risks by sex/multisite subgroups and point to a potentially important role for inflammation in OA over and above traditional CVD risk factors., (© 2021 American College of Rheumatology.)

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit. Emerging evidence from animal models of spine degeneration highlight the interdependence of IDD and facet joint OA, warranting a review of the parallels between these two degenerative phenomena for the benefit of both clinicians and research scientists. This Review discusses the pathophysiological aspects of IDD and OA, with an emphasis on tissue, cellular and molecular pathways of degeneration. Although the intervertebral disc and synovial facet joint are biologically distinct structures that are amenable to reductive scientific consideration, substantial overlap exists between the molecular pathways and processes of degeneration (including cartilage destruction, extracellular matrix degeneration and osteophyte formation) that occur at these sites. Thus, researchers, clinicians, advocates and policy-makers should consider viewing the burden and management of spinal degeneration holistically as part of the OA disease continuum., (© 2023. Springer Nature Limited.)

Objective: To determine whether an apparent association between hand osteoarthritis (OA) and adiposity is explained by the presence of OA at other joint sites., Methods: Data from the Canadian Longitudinal Study on Aging, first cycle, comprehensive cohort, were used. Respondents age 45-85 years (n = 18,279) were asked separate questions about doctor-diagnosed OA in the hand, hip, or knee. Multinomial logistic regression was used to investigate the relationship between all combinations of hand, hip, and knee OA and body mass index (BMI) and waist-to-height ratio (WHtR)., Results: OA was reported by 34.6% of respondents, 28.0% with OA at >1 joint site. Hand OA was not significantly associated with BMI after accounting for OA at other joint sites, with similar findings for WHtR. All joint site combinations containing the knee were strongly associated with BMI, with odds ratios (ORs) ranging from OR 2.92 (95% confidence interval [95% CI] 2.53-3.37) for knee OA only with obesity class I to OR 9.98 (95% CI 7.12-13.88) for multi-joint knee, hip, hand OA with obesity class II/III. BMI distributions including knee OA were broader and shifted to higher BMI levels than those for hand or hip OA., Conclusion: Apparent associations between hand OA and BMI may be explained by concurrent OA at other joint sites. Recognizing that OA is a multi-joint disease is crucial for studies of the associations of adiposity with OA in a particular joint, especially the hand. The association between knee OA and BMI appears to be distinct from those for OA at other joint sites., (© 2021 American College of Rheumatology.)

Objective: To examine the magnitude and costs of ambulatory primary care, specialist physician care, and hospital service use for musculoskeletal disorders (MSDs) in Canada's largest province, Ontario., Methods: Administrative health databases were analyzed for fiscal year 2013-2014 for adults aged ≥ 18 years, including data on physician services, emergency department (ED) visits, and hospitalizations. International Classification of Diseases diagnostic codes were used to identify MSD services. A validated algorithm was used to estimate direct medical costs. Person-visit rates and numbers of persons and visits were tabulated by care setting, age, sex, and physician specialty. Data were examined for all MSDs combined, as well as for specific diagnostic groupings., Results: Overall, 3.1 million adult Ontarians (28.5%) made over 8 million outpatient physician visits associated with MSDs. These included 5.6 million primary care visits. MSDs accounted for 560,000 (12.3%) of all adult ED visits. Total costs for MSD-related care were $1.6 billion, with 12.6% of costs attributed to primary care, 9.2% to specialist care, 8.6% to ED care, 8.5% to day surgery, and 61.2% associated with inpatient hospitalizations. Costs due to arthritis accounted for 40% of total MSD care costs ($639 million). MSD-related imaging costs were $169 million, yielding a total cost estimate of $1.8 billion for MSDs overall., Conclusion: MSDs place a significant and costly burden on the healthcare system. Health system planning needs to consider the large and escalating demand for care to reduce both the individual and population burden., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Patient satisfaction is an important indicator used to monitor quality of care and outcomes after spine surgery., Objective: To examine the complex relationship between preoperative expectations, fulfillment of expectations, postsurgical outcomes, and satisfaction after spine surgery., Methods: In this national study of patients undergoing elective surgery for degenerative spinal conditions from the Canadian Spine Outcomes and Research Network Registry, we used logistic regression to examine the relationships between patient satisfaction with surgery (1-5 scale), preoperative expectation score (0 = none to 100 = highest), fulfillment of expectations, and disability and pain improvement., Results: Fifty-eight percent of patients were extremely satisfied, and 3% were extremely dissatisfied. Expectations were variable and generally high (mean 79.5 of 100) while 17.3% reported that none of their expectations were met, 49.8% reported that their most important expectation was met, and 32.9% reported that their most important expectation was not met but others were. The results from the fully adjusted ordinal logistic model for satisfaction indicate that satisfaction was higher among patients with higher preoperative expectations (odds ratio [OR] [95% CI]: 1.11, [1.04-1.19]), reporting important improvements in disability (OR [95% CI]: 2.52 [1.96-3.25]) and pain (OR [95% CI]: 1.64 [1.25-2.15]) and reporting that expectations were fulfilled (OR = 80.15, for all expectations were met). The results were similar for lumbar and cervical patients., Conclusion: Given the dominant impact of expectation fulfillment on satisfaction level, there is an opportunity for improving overall patient satisfaction by specifically assessing and mitigating the potential discrepancies between patients' preoperative expectations and likely surgical outcomes. The findings are likely relevant across elective surgical populations., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Objective: To understand differences between people with arthritis who do not know their type (DK) compared to those reporting osteoarthritis (OA) or inflammatory and autoimmune types of arthritis (IAA), including the receipt of appropriate health care, information, and services., Methods: Analysis of the Survey on Living with Chronic Disease in Canada-Arthritis Component. Respondents aged ≥20 years with health professional-diagnosed arthritis (n = 4,385) were characterized as reporting DK, OA or IAA. Variables: arthritis characteristics (duration, number and site of joints affected), arthritis impact (current pain and fatigue, difficulty in sleeping and daily activities, impact on life), health (self-rated general and mental health, life stress), arthritis management strategies (seeing health professionals, medication use, assistive devices, receipt of arthritis information, self-management activities). Multinomial logistic and log-Poisson regressions were used, as appropriate, to compare the DK to the OA and IAA groups., Results: In this arthritis sample, 44.2% were in the DK group, 38.3% reported OA and 17.5% reported IAA. Those in the DK group were more likely to be younger, have low income, low education, and be of non-white cultural background compared to those with OA. There were no significant differences in arthritis impact, but the DK group was less likely to have received information on, or have used, arthritis management strategies., Conclusions: The sociodemographic characteristics of the DK group suggest they likely have lower health literacy. They were less likely to have accessed health care and other support services, indicating this is an important group for health education, both for individuals with arthritis and health care providers., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Up to 30% of spine facet osteoarthritis patients with lumbar spinal stenosis (SF-OA ​+ ​LSS) have little to no improvement in their pain after surgery. Lack of meaningful improvement in pain following surgery provides a unique opportunity to identify specific predictive biomarker signatures that might be associated with the outcomes of surgical treatment. The objective of the present study was to determine whether a microRNA (miRNA) biomarker signature could be identified in presurgical blood plasma that corresponded with levels of SF-OA ​+ ​LSS patient post-surgical pain intensity one year later., Methods: RNA was extracted from baseline plasma of SF-OA ​+ ​LSS patients and prepared for miRNA sequencing. Statistical approaches were performed to identify differentially expressed miRNAs associated with reduced 1-year postsurgical pain (n ​= ​56). Using an integrated computational approach, we further created predicted gene and pathway networks for each identified miRNA., Results: We identified a panel of 4 circulating candidate miRNAs (hsa-miR-155-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-99b-5p) with higher levels at presurgical baseline that were associated with greater changes in % NPRS20Δ, reflecting reduced pain intensity levels at one year. Genes encoding hsa-let-7e-5p, hsa-miR-125a-5p, and hsa-miR-99b-5p are part of an evolutionarily conserved miRNA cluster. Using integrated computational analyses, we showed that mammalian target of rapamycin, transforming growth factor-β1 receptor, Wnt signaling, epithelial-mesenchymal transition regulators, and cholecystokinin signaling were enriched pathways of predicted gene targets., Conclusions: Taken together, our findings suggest that 4 presurgical baseline circulating miRNAs correlate with 1-year postsurgical SF-OA ​+ ​LSS patient pain intensity and represent possible candidate biomarker signature of surgical pain response., Competing Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2022 The Authors.)

Objective: To evaluate a stratified screening process for the early identification of axial spondyloarthritis (SpA) with consideration of the following: 1) wait times from primary care to rheumatology screen, 2) incremental precision and accuracy from primary care to rheumatology screening, and 3) diagnostic delay., Methods: Adults with low back pain attending primary care at low back pain clinics prospectively underwent a primary standardized clinical screening. Patients with low back pain of >3 months who experienced symptom onset at age <50 years were referred for a comprehensive secondary screening by a physical therapist with advanced rheumatology training. At secondary screening, patients with features of inflammation were classified as being at a low, medium, or high risk for axial SpA versus no risk for axial SpA. Precision and accuracy of this screening strata were measured against a rheumatologist with expertise in axial SpA., Results: Overall, 405 patients underwent primary and secondary screening in the present study. The study cohort had a mean ± SD age of 36.9 ± 9.9 years, and 55% were women. HLA-B27 was present in 14.4% of patients. Median wait time from primary screening to secondary screening was 15 days. Axial SpA risk assignment by rheumatologist was 64.9% for no risk or low risk for axial SpA and 35.1% for medium risk or high risk for axial SpA. The best combination of sensitivity (68%), specificity (90%), positive predictive values (80%), and negative predictive values (84%) was evident in the secondary screening. In this cohort, 15.6% of patients received a final diagnosis of axial SpA. Median low back pain duration from symptom onset to diagnosis was 2 years for nonradiographic axial SpA and 7 years for ankylosing spondylitis., Conclusion: A stratified interprofessional screening process can facilitate rapid diagnosis of persistent low back pain with high precision and accuracy in patients who have axial SpA., (© 2021 American College of 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).)

Background: Low back pain (LBP) is a leading cause of disability globally. Risk-stratification systems (e.g. STarT Back) have been proposed to guide treatment, but with varying success. We investigated factors associated with poor response to standardized LBP education and self-management recommendations stratified by dominant pain location (back or leg)., Methods: LBP patients underwent a standardized primary care model of care of education and self-management recommendations. Poor response was defined as an Oswestry Disability Index (ODI) change score <10 units by 6 months. Multivariable logistic regression was used to identify poor response risk factors, stratified by back-dominant and leg-dominant back pain. Baseline factors: age, sex, body mass index, ODI, LBP/leg-pain intensity, LBP/leg-pain duration, STarT Back chronicity-risk, smoking, comorbidity count, and self-efficacy., Results: The sample consisted of 767 patients (443 back-dominant, 324 leg-dominant). Mean age was 53 years, and 59% were female. Females accounted for 66% of back-dominant and 50% of leg-dominant patients. Chronicity risk was 'high' for 18% of back-dominant and 29% of leg-dominant patients. Poor response was higher in back- (57%) compared to leg-dominant (42%) patients. Adjusted stratified analyses: female sex, moderate or high chronicity-risk, and increasing age were associated with increased risk of poor response, and greater self-efficacy with favourable response, in leg-dominant patients; these were not the cases among back-dominant patients. Increased comorbidity count was associated with poor response in back dominant patients. In both patient groups, higher baseline ODI score was associated with favorable response, and smoking and longer pain duration with poor response., Conclusions: Differences in the influence of sex and chronicity risk in particular on outcome by dominant pain location suggests that considering these patients as a single group may not be appropriate. Furthermore, findings suggest that stratification by pain dominance may enhance the use of established risk stratification tools such as the STarT Back., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s). Published by Elsevier Ltd on behalf of North American Spine Society.)

Objective: The focus on disability in osteoarthritis (OA) has largely been on the ability to perform specific activities, which neglects the greater implications for social participation. We investigated the association between OA and social participation, considering activity limitations and instrumental supports as intervening variables in the association., Methods: Data were from 21,214 respondents, ages 45-85 years, from cycle 1 of the Canadian Longitudinal Study on Aging. The questionnaire elicited information regarding self-reported doctor-diagnosed OA, difficulty with 14 activities, perceived availability and receipt of instrumental supports, and 17 social participation activities. Structural equation modeling was used. The primary outcome was social participation, and the primary predictor was OA. The intervening variables included activity limitations, received instrumental supports, and perceived instrumental supports. Latent variables were developed for intervening and social participation variables. The covariates included age, sex, body mass index, income, education, smoking, and comorbidity count., Results: The mean age of the respondents was 63 years, 51% were female, and 26.5% reported having OA. Two distinct social participation indicators were identified, including social participation-diversity and social participation-intensity. When intervening variables were not considered, minimal/no association was found between OA and social participation. When intervening variables were considered, unique pathways linking OA and social participation were found. The overall negative association between activity limitations and social participation was partially direct and partially buffered by both receipt of and perceived availability of instrumental supports. In the absence of activity limitations, OA was associated with greater social participation., Conclusion: Enhanced social participation in people with OA who do not have activity limitations may reflect proactive steps taken by those with mild OA to maintain activity and social engagement. For those with activity limitations, findings highlight the need for interventions to mitigate limitations and draw particular attention to the importance of both provision and awareness of available instrumental supports in maintaining social participation., (© 2020, American College of Rheumatology.)

Objective: Despite the joint pain and significant dysfunction that characterizes arthritis, many people with arthritis continue to carry out everyday duties and responsibilities. The objective of the present study was to describe participation in informal caregiving (unpaid assistance to someone with a health issue or limitation) among people with arthritis., Methods: Analysis of baseline data from the Canadian Longitudinal Study on Aging (CLSA), a nationally representative sample of people ages 45-85 years (n = 21,241), was performed. A questionnaire covering sociodemographic, health, and caregiving variables was completed by each study participant. Caregiving variables examined characteristics of the person who received the most care from the questionnaire respondent, as well as the types of caregiving (e.g., hands-on versus hands-off tasks) and amount of care provided (e.g., hours per week)., Results: There was no difference in the proportion of people with and without arthritis who provided informal care (46%). Individuals with arthritis reported worse health, but this did not affect the likelihood of providing care, nor the types or amount of care provided. Caregivers with and without arthritis were most likely to provide fewer than 7 hours per week of care, and the most common type of care was characterized as hands-off, particularly transportation assistance. Men were just as likely to provide care as women but were less likely to provide high intensity care or perform hands-on tasks., Conclusion: Despite reporting worse health on average, people with arthritis were just as likely as people without arthritis to provide informal care. The need to provide informal care among people with arthritis may impact their ability to engage in self-management activities for their arthritis., (© 2020, American College of Rheumatology.)

Introduction: Diversion of prescription opioid medication is a contributor to the opioid epidemic. Safe handling practices can reduce the risk of diversion. We aimed to understand: 1) if orthopaedic patients received instructions on how to safely handle opioids, 2) their typical storage/disposal practices, and 3) their willingness to participate in an opioid disposal program (ODP)., Methods: Cross-sectional study of adult orthopaedic patients who completed an anonymous survey on current or past prescription opioid use, instruction on handling, storage and disposal practices, presence of children in the household, and willingness to participate in an ODP. Frequencies and percentages of responses were computed, both overall and stratified by possession of unused opioids., Results: 569 respondents who reported either current or past prescription opioid use were analyzed. 44% reported receiving storage instructions and 56% reported receiving disposal instructions from a health care provider. Many respondents indicated unsafe handling practices: possessing unused opioids (34%), using unsafe storage methods (90%), and using unsafe disposal methods (34%). Respondents with unused opioids were less likely to report receiving handling instructions or using safe handling methods, and 47% of this group reported having minors or young adults in the household. Respondents who received storage and disposal instructions were more likely to report safe storage and disposal methods. Seventy-four percent of respondents reported that they would participate in an ODP., Conclusion: While many orthopaedic patients report inadequate education on safe opioid handling and using unsafe handling practices, findings suggest targeted education is associated with better behaviours. However, patients are willing to safely dispose of unused medication if provided a convenient option. These findings suggest a need to address patient knowledge and behavior regarding opioid handling to reduce the risk of opioid diversion., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Y. Raja Rampersaud has received royalties from Medtronic and holds investments in Arthur Health Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other co-authors have no competing interests to report.

Introduction: Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear., Objectives: The objectives of this retrospective study were to determine the analgesic benefits of adding a combination of perineural local anesthetic and steroids (LA-S) to CMM compared with CMM alone in patients who had moderate-to-severe refractory NP after trauma to the ankle and the foot., Methods: Health care records of 60 patients in exposed (3 injections of perineural LA-S at weekly intervals with CMM) and 60 in unexposed (CMM) cohorts were reviewed. Data on patient characteristics, pain, and mental and physical function were extracted at baseline and at the postintervention follow-up. Data were analyzed to evaluate analgesic benefit from the study interventions and the impact of baseline characteristics., Results: Perineural LA-S with CMM cohort had lower pain numerical rating scale scores at 1 to 3 months after the intervention as compared to the CMM alone cohort (5.50 [interquartile range 4.00-7.00] and 7.00 [interquartile range 5.00-8.00], respectively; P < 0.01). However, multivariable analysis did not show an independent beneficial analgesic effect with the addition of perineural LA-S to CMM compared with CMM alone. A greater severity of preintervention catastrophizing (each unit increase in pain catastrophizing score increased pain score at follow-up by 0.04, 95% confidence interval: 0.01-0.07) was associated with reduction in the analgesic benefit., Conclusion: Perineural local anesthetic and steroid injections do not confer an analgesic benefit for trauma- or compression-related peripheral NP., Competing Interests: The authors have no conflicts of interest to declare. This research was supported by the Outcomes Measurement and Research Division of Altum Health, University Health Network. The authors would like to acknowledge the help from Sabeeh Alvi and Jamal Kara (Research Coordinators) in collecting data for this study.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Objective: Patients undergoing spine surgery generally have high expectations for improvement postoperatively. Little is known about how these expectations are affected by the diagnosis. The purpose of this study was to examine whether preoperative expectations differ based on diagnostic pathoanatomical patterns in elective spine surgery patients., Methods: Patients with common degenerative cervical/lumbar pathology (lumbar/cervical stenosis, lumbar spondylolisthesis, and cervical/lumbar disc herniation) who had given their consent for surgery were analyzed using the Canadian Spine Outcomes and Research Network (CSORN). Patients reported the changes they expected to experience postoperatively in relation to 7 separate items using a modified version of the North American Spine Society spine questionnaire. Patients were also asked about the most important item that would make them consider the surgery a success. Sociodemographic, lifestyle, and clinical variables were also collected., Results: There were 3868 eligible patients identified within the network for analysis. Patients with lumbar disc herniation had higher expectations for relief of leg pain compared with stenosis and lumbar degenerative spondylolisthesis cohorts within the univariate analysis. Cervical stenosis (myelopathy) patients were more likely to rank general physical capacity as their most important expectation from spine surgery. The multinomial regression analysis showed that cervical myelopathy patients have lower expectations for relief of arm or neck pain from surgery (OR 0.54, 0.34-0.88; p < 0.05). Patient factors, including age, symptoms (pain, disability, depression), work status, and lifestyle factors, were significantly associated with expectation, whereas the diagnoses were not., Conclusions: Patients with degenerative spinal conditions consenting for spine surgery have high expectations for improvement in all realms of their daily lives. With the exception of patients with cervical myelopathy, patient symptoms rather than diagnoses had a more substantial impact on the dimensions in which patients expected to improve or their most important expected change. Determination of patient expectation should be individualized and not biased by pathoanatomical diagnosis.

Background Context: In the lumbar spine osteoarthritis (LS-OA) population having surgery for lumbar spinal stenosis (LSS) symptoms, a significant proportion of patients experience limited benefit following the intervention. Thus, identifying contributing factors to this is important. Individuals with OA often have multiple joint symptoms, yet this has received limited attention in this population., Purpose: Document the occurrence of joint symptoms among patients undergoing surgery for LS-OA, and investigate the influence of these symptoms on disability postsurgery., Design: Prospective study of consecutive patients followed to 12-month postsurgery., Patient Sample: Patients undergoing surgery (decompression surgery, with or without fusion) for neurogenic claudication with or without back pain due to LSS with a primary pathology diagnosis of LS-OA., Outcomes Measures: Patient self-reported: Oswestry Disability Index (ODI), completed pre- and 12-month postsurgery; and, completed presurgery, age, sex, education, smoking, comorbid conditions, opioid use, short/long-term disability, depression and anxiety symptoms, back and leg pain intensity, presence of spondylolisthesis, procedure, prior spine surgery, and joints with arthritis and "pain/stiffness/swelling most days of the month" indicated on a homunculus (a joint site count was derived)., Assessments: Height and weight, used to calculate body mass index; timed-up-and-go performance-based test., Methods: Outcome of interest was achieving a clinically important improvement (CII) in ODI by 12-month postsurgery (yes/no). The association between joint site count and achieving a CII was examined by multivariable logistic regression analyses, adjusted for other measures., Results: In all, 165 patients were included. The mean age was 67 years (range: 44-90) and 47% were female. Seventy-seven percent reported 1+ joint site other than the back, 62% reported 2+, and 25% reported 4+. Among those achieving a CII, 21% had 4+ joint sites, compared with 31% among those not achieving a CII. Adjusted analyses: Increasing joint site count was associated with increasing risk (odds ratio [OR]: 1.32, 95% confidence interval [CI]: 1.05, 1.66) of not achieving a CII; for those with 4+ joints, adjusted probability of not achieving a CII exceeded 50%. Also associated with an increased risk of not achieving a CII was presurgery anxiety (OR: 2.97, 95% CI: 1.02, 8.65), opioid use (OR: 2.89, 95% CI: 1.07, 7.82), and worse back pain intensity score (OR: 1.27, 95% CI: 1.05, 1.53)., Conclusions: Multijoint involvement was highly prevalent in this LS-OA surgical sample. Its association with poorer postsurgery outcome supports a comprehensive approach to OA management and care. Knowledge of multijoint symptoms should inform patient education, shared decision-making, and recommendations for postsurgical rehabilitation and self-management strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren-Lawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state., Design: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs., Results: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms., Conclusion: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the association of OA risk factors with number of painful joint sites in a representative population sample., Methods: Analysis of the 2009 Survey on Living with Chronic Diseases in Canada - Arthritis Component (n = 1614) for respondents reporting symptomatic OA. Variables: painful joints sites (hands, wrists, elbows, shoulders, hips, knees, ankles, feet, back, neck), joint symptom duration, sociodemographic characteristics, smoking, comorbidities and BMI. Zero-truncated negative binomial regressions were used to investigate the association between number of painful joint sites and the variables. Generalizability of findings was assessed by a similar analysis in a clinical hip/knee OA sample., Results: The sample comprised 73% women and 56% were aged <65 years. The mean number of painful joint sites was 3.8: 84% reported pain at ≥2 sites, and 45% at ≥4 sites. Age, BMI, education and smoking were not associated with the number of joint sites. Significant associations were found with being female [rate ratio (RR) = 1.23, 95% CI 1.09, 1.39], having more comorbidities (RR = 1.11, 95% CI 1.07, 1.15) and longer symptom duration (RR = 1.16, 95% CI 1.09, 1.24), although the increase in joint sites with duration was small. Similar regression results were found with the clinical OA sample., Conclusion: The lack of an association of age and BMI (obesity) with number of painful joint sites in OA raises questions about the role of these risk factors and our understanding of OA as a multi-joint disease. Filling this knowledge gap is critical to making progress with defining OA phenotypes and identifying potential aetiological mechanisms., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for 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.)

Study Design: Cross-sectional, pre-post patient survey., Objective: The aim of this study was to determine what factors affect a patient's decision to undergo elective surgery following a surgical consultation., Summary of Background Data: The surgical consultation is an important step in selecting and preparing patients for elective surgery. Despite the proven effectiveness and low risk of complications, many spine procedure candidates may still choose to forgo surgery after an appropriate discussion and clear surgical indications., Methods: Survey and open-response questions regarding pre- and post-consultation surgical concerns and overall willingness to undergo surgery were collected and analyzed from 124 patients deemed surgical candidates. Demographics, surgical willingness, and patient concerns were analyzed. Open-ended response data were tallied for surgical concerns and responses were analyzed line-by-line to assess for main themes. Sub-analysis was included on patients who reconsidered their willingness post-consultation., Results: Qualitative thematic analysis of patient's concerns regarding surgery uncovered six major themes: Interference on quality of life (QOL), fear, physical concerns, success, risk, and concerns regarding the surgeon (CS). Success and risk were most commonly mentioned pre-consultation (27%, 26%); risk and QOL were most commonly mentioned post-consultation (22%, 21%). Of 124 patients, 103 were willing to have surgery before consultation and remained willing post-consultation; six patients became unwilling. Twenty-one patients were unwilling to consider surgery before consultation; only five remained unwilling. No differences were found between degenerative and deformity patients regarding initial willingness or changes thereafter., Conclusion: The decision to undergo surgery is a multifactorial and complex process with a variety of patient concerns. We grouped these concerns into six categories to aid in future discussion with patients. 87% of patients have made up their mind before attending their surgical consultation. Appropriate understanding of patient-specific willingness and concerns should help facilitate necessary discussion and aid in a more efficient and useful shared decision-making process., Level of Evidence: 4.