Total Hip Arthroplasty Versus Education and Exercise: A Propensity-Matched Analysis of 266 Patients Who Have Hip Osteoarthritis.

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.

Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients.

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.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

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.

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints.

OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration. METHODS: We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. RESULTS: miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

Understanding the Relationship Between 3-Month and 2-Year Pain and Function Scores After Total Knee Arthroplasty for Osteoarthritis.

BACKGROUND: Research to understand predictors of poor outcomes after total knee arthroplasty (TKA) has largely focused on presurgery factors. We examined whether pain and function 3-month postsurgery were predictive of longer-term outcomes ascertained 2 years after TKA. METHODS: Western Ontario McMaster University Osteoarthritis Index pain and physical function scores (scaled 0-20 and 0-68; higher = worse) were recorded pre-TKA and 3, 12, and 24 months post-TKA. A sequential series of regression models was used to examine the relative contribution of baseline score and baseline to 3-month and 3 to 12-month change score to explaining variability (R2) in 2-year pain and function scores, with consideration for presurgery covariates. RESULTS: Data from 560 patients were analyzed. Mean pain and function scores improved significantly presurgery to 2 years postsurgery; 10-4 and 33-16 (P < .001), respectively. Considerable variability in 2-year scores was observed. Overall, 80.3% and 79.9% of changes in pain and function scores over the 2 years occurred within the first 3 months. Change over these 3 months explained the greatest proportion of variability in 2-year scores, 16% and 23% for pain and function, respectively. The influences of these early changes were similar to those of baseline status. CONCLUSION: Changes in patient-reported pain and function occurring within the first 3 months post-TKA strongly determine pain and function status at 2 years. Research to identify pre-/intra-/early postoperative factors associated with change in this early postoperative period that may be amenable to modification or used to better inform education and decision-making is warranted.

PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage.

OBJECTIVES: We have previously shown that peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor, is essential for the normal growth and development of cartilage. In the present study, we created inducible cartilage-specific PPARγ knockout (KO) mice and subjected these mice to the destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to elucidate the specific in vivo role of PPARγ in OA pathophysiology. We further investigated the downstream PPARγ signalling pathway responsible for maintaining cartilage homeostasis. METHODS: Inducible cartilage-specific PPARγ KO mice were generated and subjected to DMM model of OA. We also created inducible cartilage-specific PPARγ/mammalian target for rapamycin (mTOR) double KO mice to dissect the PPARγ signalling pathway in OA. RESULTS: Compared with control mice, PPARγ KO mice exhibit accelerated OA phenotype with increased cartilage degradation, chondrocyte apoptosis, and the overproduction of OA inflammatory/catabolic factors associated with the increased expression of mTOR and the suppression of key autophagy markers. In vitro rescue experiments using PPARγ expression vector reduced mTOR expression, increased expression of autophagy markers and reduced the expression of OA inflammatory/catabolic factors, thus reversing the phenotype of PPARγ KO mice chondrocytes. To dissect the in vivo role of mTOR pathway in PPARγ signalling, we created and subjected PPARγ-mTOR double KO mice to the OA model to see if the genetic deletion of mTOR in PPARγ KO mice (double KO) can rescue the accelerated OA phenotype observed in PPARγ KO mice. Indeed, PPARγ-mTOR double KO mice exhibit significant protection/reversal from OA phenotype. SIGNIFICANCE: PPARγ maintains articular cartilage homeostasis, in part, by regulating mTOR pathway.

Stem cell therapy for the treatment of early stage avascular necrosis of the femoral head: a systematic review.

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.

High health care use prior to elective surgery for osteoarthritis is associated with poor postoperative outcomes: A Canadian population-based cohort study.

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.

The impact of diabetes status on pain and physical function following total joint arthroplasty for hip and knee osteoarthritis: variation by sex and body mass index.

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.

The impact of diabetes on physical and mental health status and patient satisfaction after total hip and knee arthroplasty.

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.

Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity-Matched Analysis.

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.

Measuring expectations in orthopaedic surgery: a systematic review.

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.

The role of surgeon volume on patient outcome in total knee arthroplasty: a systematic review of the literature.

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.

A pilot study of computed tomography-detected asymptomatic pulmonary filling defects after hip and knee arthroplasties.

We asked what the incidence of asymptomatic filling defects is on routine multidetector computed tomography (MDCT) in primary hip (total hip arthroplasty [THA]) and knee arthroplasties (TKA) patients. We prospectively performed MDCT scans on the first postoperative day for THA (n = 21)/TKA (n = 27). Patients underwent routine postoperative care, and data were collected for symptoms such as tachycardia or shortness of breath. More patients undergoing TKA had positive computed tomography scans than those undergoing THA: 11 (41%) vs 1 (5%), respectively. All patients diagnosed with a filling defect were discharged from the hospital without treatment of symptomatic pulmonary embolism. Our study demonstrates a high rate of abnormal MDCT early after lower extremity arthroplasty, the clinical importance of which may be benign.

Comparison of arthroplasty trial publications after registration in ClinicalTrials.gov.

In 2005, the International Committee of Medical Journal Editors established a mandatory trial registration before study enrollment for publication in member journals. Our primary objective was to evaluate the publication rates of arthroplasty trials registered with ClinicalTrials.gov (CTG). We further aimed to examine the consistency of registration summaries with that of final publications. We searched CTG for all trials related to joint arthroplasty and conducted a thorough search for publications resulting from registered closed trials. Of 101 closed and completed trials, we found 23 publications, for an overall publication rate of 22.8%. Registration of arthroplasty trials in CTG does not consistently result in publication or disclosure of results. In addition, changes are frequently made to the final presentation of the data that are not reflected in the trial registry.

Identification of a differential metabolite-based signature in patients with late-stage knee osteoarthritis.

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 â€‹= â€‹67.58 years) non-diabetic, non-obese (BMI <30 â€‹kg/m2, mean â€‹= â€‹26.25 â€‹kg/m2), 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 â€‹< â€‹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 â€‹= â€‹0.921). Fifty-six genes were linked to at least 2 â€‹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.

Healthcare Utilization and Costs for Musculoskeletal Disorders in Ontario, Canada.

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.

Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity.

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/m2, 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.

Comparison of published orthopaedic trauma trials following registration in Clinicaltrials.gov.

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.

Meta-analysis and systematic review of clinical outcomes comparing mobile bearing and fixed bearing total knee arthroplasty.

Mobile bearing (MB) knee replacements were designed with the goal of increased conformity and decreased bearing wear. We conducted a meta-analysis and systematic review of randomized controlled trials comparing outcomes of MB and fixed bearing (FB) total knee arthroplasty (TKA). We identified 14 studies reporting our primary outcome of Knee Society Scores (KSS). We also pooled data for post-operative range of motion (ROM) and Hospital for Special Surgery scores (HSS). The standard difference in mean outcome scores for KSS and HSS demonstrated no difference between groups (P = .902, and P = .426 respectively). Similarly, the pooled data for ROM showed no difference between groups (P = .265). The results of this study found no significant differences between clinical outcomes of MB and FB TKA.