Predictive Factors of Pain and Functional Outcome 5 Years Following Total Hip Arthroplasty: A Prospective Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement Cohort Study.

BACKGROUND: Previous reports have identified a number of potential predictors of pain and function after total hip arthroplasty (THA). However, the results of these studies were conflicting, and most had a short follow-up after THA. The purpose of this study was to identify factors predictive of pain and function 5 years after THA. METHODS: A multicenter cohort of 7,934 primary unilateral THA patients was prospectively enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement consortium. Demographic data, comorbidities, and patient-reported outcome measures were collected preoperatively and postoperatively at 5 years, including the Hip Disability and OSteoarthritis Outcome Score (HOOS) pain and activities of daily living (ADL) scores. Multivariate logistic regression models with 95% confidence interval were used to identify independent predictors of pain and function at 5 years. RESULTS: The patient dissatisfaction percentage was 8.2% at 5 years after THA. The multivariate regression identified the following predictive factors for the HOOS pain score at 5 years: age, educational level, insurance, smoking, race, Charlson Comorbidity Index, back pain severity, number of other lower extremity painful joints, the Knee Injury and Osteoarthritis Outcome Score pain severity of the ipsilateral knee, preoperative Short-Form Health Survey 36-item (SF-36) mental component summary score, and HOOS pain scores. The multivariate regression identified the following predictor factors for HOOS ADL score at 5 years: body mass index, insurance, smoking, race, back pain severity, number of other lower extremity painful joints, Knee Injury and Osteoarthritis Outcome Score pain severity of ipsilateral knee, preop HOOS ADL, and preoperative SF-36 mental component summary score and SF-36 physical component summary score. CONCLUSIONS: Overall, 8.2% of patients were dissatisfied 5 years after primary THA. We have identified a number of factors that predict less improvement in pain and function 5 years after THA. These potentially modifiable factors can be targeted with preoperative patient optimization programs to improve patient outcomes and satisfaction after primary THA. Knowledge of these factors that predict less improvement in pain and function can assist the surgeon and patient during shared decision-making, and in setting appropriate patient expectations preoperatively.

Gender Differences in Pain, Function, and Quality of Life Five Years Following Primary Total Knee Arthroplasty.

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcomes after total knee arthroplasty (TKA). The impact of gender on outcomes after TKA remains controversial. Previous studies had less than 5 years of follow-up after TKA. The aim of this evaluation was to determine what differences in pain, function, and quality of life (QoL) exist between female and male patients 5 years after primary TKA. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients (7,284 females and 4,318 males) was prospectively evaluated. All patients were enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. Demographic data, musculoskeletal and medical comorbid conditions, and patient-reported outcome measures, including the Knee Injury and Osteoarthritis Outcome (KOOS) and Short-Form (36-item) Health Survey mental component score (MCS) and physical component score (PCS) were collected preoperatively and at 5 years after TKA. Descriptive statistics were generated, and stratified by gender, and differences in pain, function, and QoL between female and male patients were evaluated. Multivariate regression models with a 95% confidence interval (CI) were used to assess the role of patient gender as a predictive factor for KOOS pain and function in daily living (ADL) scores reported 5 years after primary TKA, while adjusting for other variables. RESULTS: Prior to surgery, female patients reported worse pain (KOOS pain 46 versus 52), function (KOOS ADL 53 versus 59), and QoL (KOOS QoL 26 versus 29) than male patients. The differences in preoperative scores ranged from 2.70 (KOOS QoL) to 6.12 (KOOS ADL). At 5 years after TKA, female patients reported slightly worse pain (87 versus 89), function (85 versus 87), and QoL (74 versus 75) when compared to male patients. The differences in the mean 5-year postoperative KOOS scores (range, 0.99 to 2.73), although statistically significant (P < .001), were clinically negligible. Female patients achieved greater improvement in pain (41 versus 37), function (32 versus 29), and QoL (48 versus 46) scores in comparison to male patients. Female patients also reported lower preoperative PCS global function (33 versus 35) scores, 5-year postoperative PCS scores (45 versus 46), and MCS global mental function scores (52 versus 54). Similarly, the differences in the 5-year postoperative Short-Form (36-item) Health Survey MCS and PCS scores were clinically negligible. Multivariate regression analysis showed that female gender was not independently predictive for either pain (ß = -1.08; 95% CI [-1.25 to 1.03] [P = .85]) or function (ß = 0.64; 95% CI [-0.51 to 1.79] [P = .28]) 5 years after surgery. CONCLUSIONS: There are no clinically significant gender differences in pain, function, or QoL 5 years after TKA. Female patients typically have worse symptoms prior to surgery, improve more than male patients, and end up with pain, function, and QoL scores clinically equal to male patients. These data can enhance the shared decision-making process between female patients and surgeons and assist in setting appropriate patient expectations prior to TKA.

How Back Pain Affects Patient Satisfaction After Primary Total Knee Arthroplasty.

BACKGROUND: Although back pain (BP) has been shown to be a predictor of dissatisfaction after total knee arthroplasty (TKA) in some reports, these studies did not use a scale to quantify the degree of pain. The purpose of this study was to quantify the effect of BP intensity on patient satisfaction reported at 1 year after TKA. METHODS: A multicenter prospective cohort was taken in which 9,057 patients undergoing primary unilateral TKA were enrolled in FORCE-TJR and demographic and clinical data were collected. Back pain (BP) intensity was assessed using the Oswestry back disability index (ODI) pain intensity questionnaire. Patients were classified into 4 categories based on the severity of BP. Patient-reported outcomes (PROs) were collected preoperatively and postoperatively after 1 year including the Knee injury and Osteoarthritis Outcome Score (KOOS) (total score, pain, Activities of Daily Living (ADL), and Quality of Life (QOL), Short-Form health survey 36-item (SF-36) Physical Component Score (PCS), and Mental Component Score (MCS)). We used a validated 5-point Likert satisfaction scale. Univariate analyses of the difference between the satisfied and dissatisfied patients' groups was performed. Multivariate logistic regression models with 95% confidence interval (CI) were used to quantify the effect of BP intensity on patient dissatisfaction at 1 year. Receiver operating characteristic (ROC) analyses were performed with measurement of area under curve (AUC). RESULTS: At 1 year, a total of 1,657 TKA patients (18.3%) were dissatisfied. A total of 4,765 patients (52.6%) reported back pain at the time of surgery, including mild BP in 2,264 patients (24.9%), moderate BP in 1,844 patients (20.3%), and severe BP in 657 patients (7.2%). Severe back pain was significantly associated with patient dissatisfaction at 1 year after TKA (P = .0006). The multivariate regressions showed that patients who had severe BP were 1.6 times more likely to be dissatisfied when compared to patients who had no BP [odds ratio (OR) 1.63; 95% confidence interval (CI) (1.23-2.16), P = .0006]. While patients who had mild BP [OR 0.98; 95% CI (0.82-1.17), P = .87] or moderate BP [OR 0.97; 95% CI (0.80-1.18), P = .78] were not associated with an increased likelihood of dissatisfaction. Other predictive variables for dissatisfaction, include age [OR for younger patients <65 years versus older patients ≥65 years, 0.74; 95% CI (0.59-0.92)], educational level [OR for post high school versus less, 0.83; 95% CI (0.71, 0.97)], smoking [OR for nonsmoker versus current smoker, 0.63; 95% CI (0.45, 0.87)], and Charlson comorbidity index [OR for CCI ≥2 versus 0, 1.25; 95% CI (1.05, 1.49)]. CONCLUSION: Increased BP intensity was associated with increased risk of dissatisfaction 1 year after TKA. Only patients who had severe BP were 1.6 times more likely to be dissatisfied. The data presented here can help to improve shared decision-making and patient counseling before surgery. Surgeons should consider a spine evaluation in patients who have severe BP prior to TKA.

Age-Related Differences in Pain, Function, and Quality of Life Following Primary Total Knee Arthroplasty: Results From a FORCE-TJR (Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement) Cohort.

BACKGROUND: The impact of age on patient outcomes after total knee arthroplasty (TKA) remains controversial. Age has shown no effect on outcome in some studies, while others have reported better or worse outcome in younger patients. The aims of this study were to determine the differences in pain, function, and quality of life (QoL) reported 1 year after TKA across different age groups. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients was evaluated. Demographic data, comorbid conditions, and patient-reported outcome measures including the knee injury and osteoarthritis outcome score (KOOS), KOOS-12, KOOS Joint Replacement, and Short-Form health survey (12-item) were collected preoperatively and at 1-year postoperatively. Descriptive statistics were generated, stratified by age [<55 years (younger adult), 55 to 64 years (older adult), 65 to 74 years (early elder), and ≥ 75 years (late elder)], and differences in pain, function, and QoL among the 4 age groups were evaluated using Chi-square and Kruskal-Wallis tests. Multivariate regression models with 95% confidence interval were performed to determine if age was predictive for KOOS pain and function scores. RESULTS: Prior to surgery, younger patients (<55 years) reported worse KOOS pain (39), function (50), and QoL (18) scores with poor mental health score (47) than other older patient groups. The mean preoperative score differences across the age groups in the KOOS total score (9.37), KOOS pain (11.61), KOOS-12 pain (10.14), and KOOS/KOOS-12 QoL (12.60) reached the calculated minimal clinically important difference. At 1 year after TKA, younger patients (<55 years) reported lower KOOS pain, function, and QoL scores when compared to older patients (≥ 75 years). The differences in 1-year postop scores among the 4 age groups (ranging from 4.0 to 12.2) reached the minimal clinically important difference for pain (10.4) and QoL (12.2). Younger patients (<55 years) achieved higher baseline to 1-year pain (36.8 points), function (30.3 points), and QoL (40.7 points) score changes when compared to older patients aged ≥ 75 years. Although statistically significant, the differences in score changes among the age groups were clinically irrelevant. The multivariate regression analyses showed that age was a significant predictor for pain, but not for function at 1 year where KOOS pain score was predicted to be higher (less pain) (ß = 6.17; 95% confidence interval 4.12- 8.22) (P < .001) in older patients (≥ 75 years) when compared to younger patients (<55 years). CONCLUSION: A TKA provides a dramatic improvement in pain, function, and QoL in all age groups. However, there are age-related clinically significant differences in preoperative pain, QoL, and mental health and in final postoperative pain and QoL scores with younger patients (<55 years) reporting more pain, less QoL, and worse preoperative mental health. The patient-reported outcome measure data presented here can be used clinically to improve shared decision-making and patient expectations prior to TKA.

The Prevalence and Predictors of Patient Dissatisfaction 5-years Following Primary Total Knee Arthroplasty.

BACKGROUND: Previous studies have evaluated patient dissatisfaction after total knee arthroplasty (TKA) at 1 year, but there is no data about the prevalence of dissatisfaction among TKA patients after prolonged follow-up. The purpose of this study is to determine patient dissatisfaction 5-years after TKA and to identify patient factors predictive of dissatisfaction. METHODS: Demographic and clinical data on 4402 patients undergoing primary unilateral TKA between 2012 and 2015 were collected prospectively through the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) comparative effectiveness consortium including diverse community and academic practices distributed across 23 states in the United States. Data collected at 1 year preoperatively and 5 years postoperatively included patient satisfaction (using a 5-point Likert satisfaction scale) and patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score (KOOS) and Short-Form health survey (36-item). A univariate analysis of the difference between the satisfied and dissatisfied patients' groups was performed. A multivariate logistic regression model with 95% confidence interval (CI) was used to identify independent predictors of dissatisfaction at 5 years. The regression model was performed after adjusting the following variables: age, gender, body mass index (BMI), Charlson Comorbidity Index (CCI), marital status, smoking, education, and insurance type. The Receiver Operating Characteristic (ROC) analysis was performed with the measurement of area under curve (AUC). Hosmer-Lemeshow goodness of fit test was performed to evaluate the validity of the model. RESULTS: A total of 12.7% patients (559/4402) reported dissatisfaction 5-years after TKA. Increased BMI, higher CCI, higher Oswestry disability index, and increased number of other painful lower extremities (LE) joints were significantly associated with dissatisfaction. Higher rates of dissatisfaction were present in young patients, patients with less education, and non-White patients. Patient dissatisfaction was significantly associated with poor preoperative and 5-year postoperative PROMs scores and less score improvement from baseline to 5 years (P < .001). The multivariate regression analysis showed that an increased number of other painful LE joints (OR = 1.81; 95% CI (1.14-2.88) (P = .01), increased Oswestry back disability index (OR = 1.40; 95% CI (1.07-1.82) (P = .01), non-White patients (OR = 1.74; 95% CI (1.26-2.40) (P = .001), and minimal preoperative functional disability with KOOS function in daily living (ADL) score ≥70 (OR = 0.64; 95% CI (0.43-0.95) (P = .02) were independent predictive factors for dissatisfaction at 5 years. CONCLUSION: A total of 12.7% patients reported dissatisfaction 5-years after TKA. Clinical profiles of the satisfied and dissatisfied patients were captured 5-years after TKA with differences in the preoperative demographic and clinical characteristic variables identified. Risk factors for long-term patient dissatisfaction after TKA have been identified and should be considered during shared decision making while planning for TKA. Surgeons should use these identified risk factors to set realistic expectations for patients at an increased risk for dissatisfaction aiming to optimize their outcomes and increase their long-term satisfaction after TKA.

Do Patient Outcomes Vary by Patient Age Following Primary Total Hip Arthroplasty?

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcome after total hip arthroplasty (THA). Age has shown no effect on outcome in some evaluations, while others have reported higher functional improvement in younger patients. The aim of this study was to determine if outcome after THA varies based on patient age. METHODS: A prospective, multicenter cohort of 7,934 unilateral primary THA patients from the FORCE-TJR comparative effectiveness consortium was evaluated. Demographic data, comorbid conditions, and Patient-Reported Outcome Measures, including (HOOS), HOOS-12, HOOS JR, and SF-36 (PCS) and (MCS), were collected preop and at 1-year postop. Descriptive statistics were generated, stratified by age (<55 years [younger adult], 55-64 years [older adult], 65-74 years [early elder], and ≥75 years [late elder]), and differences in pain, function, and quality of life among the 4 age groups were evaluated. A multivariate regression model with 95% confidence interval (CI) was used to assess the role of patient age as a predictive factor for HOOS pain and function scores reported 1 year after primary THA. RESULTS: Prior to surgery, younger patients (<55 years) reported worse pain, function, and quality of life than the other 3 patient groups. At 1 year after THA, younger patients (<55 years) reported slightly worse pain and quality of life but better function scores than the 3 older patients' groups. Younger patients (<55 years) achieved higher baseline to 1-year pain, and function score changes when compared to the older patients' groups. The quality of life score changes was not different among the 4 age groups. The differences in 1-year postop scores (ranging from 2.74 to 8.46) and the magnitude of score changes from baseline to 1 year (ranging from 1.9 to 5.85), although statistically significant (P < .001), did not reach the minimal clinically important difference (MCID). The multivariate regression analysis shows that age is a significant predictor for pain at 1 year but not for function. Although HOOS pain score is predicted to be higher by 4.38 points (less pain) 1 year after THA in older patients (≥75), when compared to younger patients (<55 years), again the difference is well below the MCID and is clinically insignificant. CONCLUSION: Although there are statistically significant differences in pain relief, functional improvement, and quality of life between younger and older patients among different patients' age groups, there is no clinically significant difference. THA provides an improvement in quality of life by decreasing pain and increasing function in all 4 age groups, with large improvements in Patient-Reported Outcome Measures scores (>2 standard deviations) without clinically significant age-related differences in THA outcome at 1 year.

Important patient characteristics differ prior to total knee arthroplasty and total hip arthroplasty between Switzerland and the United States.

BACKGROUND: Outcomes after total knee (TKA) and hip (THA) arthroplasty are often generalized internationally. Patient-dependent factors and preoperative symptom levels may differ across countries. We compared preoperative patient and clinical characteristics from two large cohorts, one in Switzerland, the other in the US. METHODS: Patient characteristics were collected prospectively on all elective primary TKAs and THAs performed at a large Swiss hospital and in a US national sample. Data included age, sex, education level, BMI, diagnosis, medical co-morbidities, PROMs (WOMAC pain/function), global health (SF-12). RESULTS: Six thousand six hundred eighty primary TKAs (US) and 823 TKAs (Swiss) were evaluated. US vs. Switzerland TKA patients were younger (mean age 67 vs. 72 years.), more obese (BMI ≥30 55% vs. 43%), had higher levels of education, more cardiac disease. Swiss patients had lower preoperative WOMAC pain scores (41 vs. 52) but pre-operative physical disability were comparable. 4,647 primary THAs (US) and 1,023 THAs (Swiss) were evaluated. US vs. Switzerland patients were younger (65 vs. 68 years.), more obese (BMI ≥30: 38% vs. 24%), had higher levels of education, more diabetes. Swiss patients had lower preoperative WOMAC pain scores (40 vs. 48 points). Physical disability was reported comparable, but Swiss patients indicated lower mental health scores. CONCLUSION: We found substantial differences between US and Swiss cohorts in pre-operative patient characteristics and pain levels, which has potentially important implications for cross-cultural comparison of TKA/THA outcomes. Reports from national registries lack detailed patient information while these data suggest the need for adequate risk adjustment of patient factors.

Preoperative Pain and Function: Profiles of Patients Selected for Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is an effective treatment to relieve pain and restore function in patients with advanced knee osteoarthritis. TKA utilization is growing rapidly, and the appropriateness of current TKA use is of great interest. We examined patient-reported preoperative pain and function profiles to understand symptom severity at the time of TKA decision. METHODS: Data were from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. We included patients undergoing primary, unilateral TKAs between 2011 and 2014 for osteoarthritis and had data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and Short-Form 36-item Physical Component Summary (PCS) score. We compared patient profiles across groupings by symptoms: (1) little pain and high function (KOOS ≥70, PCS ≥40); (2) little pain but poor function (KOOS ≥70, PCS <40); (3) high pain but high function (KOOS <70, PCS ≥40); and (4) high pain and poor function (KOOS <70, PCS <40). RESULTS: Of 6936 patients, 77% had high pain and poor function (group 4), 19% had high pain "or" poor function (groups 2-3), and 5% had little pain and high function before TKA (group 1). In group 1, 86% were constantly aware of their knee problem, 48% reported pain daily yet 5% experienced severe or extreme pain on stairs, and 1% pain in bed. Over half had a lot of limitations in vigorous activities. Compared with group 4, group 1 were older, less obese, more educated, and included more men and people reporting being healthy, less disabled, and happy (P < .05 for all). CONCLUSION: Most patients undergoing TKAs had significant pain and/or poor function. Our results provide critical information given the current debate of potentially inappropriate TKA utilization in the United States.

Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading.

Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 functions, by examining expression in cartilage during mouse and human osteoarthritis (OA) progression and in response to mechanical loading. Spared and diseased compartments in knees of OA patients and in mice with surgical destabilization of the medial meniscus were examined for changes in expression of Runx1 mRNA (Q-PCR) and protein (immunoblot, immunohistochemistry). Runx1 levels were quantified in response to static mechanical compression of bovine articular cartilage. Runx1 function was assessed by cell proliferation (Ki67, PCNA) and cell type phenotypic markers. Runx1 is enriched in superficial zone (SZ) chondrocytes of normal bovine, mouse, and human tissues. Increasing loading conditions in bovine cartilage revealed a positive correlation with a significant elevation of Runx1. Runx1 becomes highly expressed at the periphery of mouse OA lesions and in human OA chondrocyte 'clones' where Runx1 co-localizes with Vcam1, the mesenchymal stem cell (MSC) marker and lubricin (Prg4), a cartilage chondroprotective protein. These OA induced cells represent a proliferative cell population, Runx1 depletion in MPCs decreases cell growth, supporting Runx1 contribution to cell expansion. The highest Runx1 levels in SZC of normal cartilage suggest a function that supports the unique phenotype of articular chondrocytes, reflected by upregulation under conditions of compression. We propose Runx1 co-expression with Vcam1 and lubricin in murine cell clusters and human 'clones' of OA cartilage, participate in a cooperative mechanism for a compensatory anabolic function.

Preoperative pain and function profiles reflect consistent TKA patient selection among US surgeons.

BACKGROUND: As the number of primary total knee arthroplasties (TKAs) performed in the United States increases, policymakers have questioned whether the indications and timing of TKA have evolved so that surgery is offered earlier. QUESTIONS/PURPOSES: We analyzed data from a US national TKA cohort to evaluate variation in surgeon selection criteria for elective unilateral TKA based on preoperative patient-reported pain and function scores. METHODS: Preoperative SF-36 (Physical Component Summary [PCS]/physical function) scores and Knee Injury and Osteoarthritis Outcome Score (KOOS) (pain, activities of daily living/function) of 4900 patients undergoing elective unilateral TKA enrolled in this national database of prospectively followed patients from 22 states were evaluated. The 25th, 50th, and 75th percentile pain and function scores for patients cared for in 24 orthopaedic offices with 20 or more patients in the database were compared to assess whether consistent preoperative criteria are used in selecting patients undergoing TKA across settings. RESULTS: The preoperative global function (PCS median, 32.6; national norm, 50; SD, 10) and knee-specific function (KOOS median, 51.5; maximum score, 100; SD, 17) percentile scores represented substantial patient disability, because both values approached 2 SDs below ideal. Consistency in patients across 24 surgeon offices, and more than 100 surgeons, was noted because site-specific medians varied from the national median by less than the minimum clinically important change. CONCLUSIONS: These data suggest that despite the rapidly growing use of TKA, surgeons in the participating sites use consistent patient criteria in scheduling TKA. Today's patients report significant pain and disability, supporting the need for TKA.

A Novel Method for Assessment of Polyethylene Liner Wear in Radiopaque Tantalum Acetabular Cups: Clinical Validation in Patients Enrolled in a Randomized Controlled Trial.

Conventional radiostereometric analysis (RSA) for wear is not possible in patients with tantalum cups. We propose a novel method for wear analysis in tantalum cups. Wear was assessed by gold standard RSA and the novel method in total hip arthroplasty patients enrolled in a randomized controlled trial receiving either titanium or tantalum cups (n=46). The novel method estimated the center of the head using a model based on identification of two proximal markers on the stem and knowledge of the stem/head configuration. The novel method was able to demonstrate a pattern of wear that was similar to the gold standard in titanium cups. The novel method offered accurate assessment and is a viable solution for assessment of wear in studies with tantalum cups.

Vancomycin-bearing synthetic bone graft delivers rhBMP-2 and promotes healing of critical rat femoral segmental defects.

BACKGROUND: Bone grafts simultaneously delivering therapeutic proteins and antibiotics may be valuable in orthopaedic trauma care. Previously, we developed a poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) synthetic bone graft that, when preabsorbed with 400-ng rhBMP-2/7, facilitated the functional repair of critical-size rat femoral defects. Recently, we showed that pHEMA-nHA effectively retains/releases vancomycin and rhBMP-2 in vitro. The success of such a strategy requires that the incorporation of vancomycin does not compromise the structural integrity of the graft nor its ability to promote bone healing. QUESTIONS/PURPOSES: (1) To evaluate the ability of pHEMA-nHA-vancomycin composites in combination with 3-µg rhBMP-2 to repair 5 mm rat femoral segmental defects, and (2) To determine if the encapsulated vancomycin impairs the graft/rhBMP-2-assisted bone repair. METHODS: pHEMA-nHA-vancomycin, pHEMA-nHA, or collagen sponge control with/without 3-µg rhBMP-2 were press-fit in 5 mm femoral defects in SASCO-SD male rats (289-300 g). Histology, microcomputed tomography, and torsion testing were performed on 8- and 12-week explants to evaluate the extent and quality of repair. The effect of vancomycin on the temporal absorption of endogenous BMP-2 and stromal cell-derived factor-1 was evaluated by immunohistochemistry. These factors are important for bone healing initiation and stem cell recruitment, respectively. RESULTS: Partial bridging of the defect with bony callus by 12 weeks was observed with pHEMA-nHA-vancomycin without rhBMP-2 while full bridging with substantially mineralized callus and partial restoration of torsional strength was achieved with 3-µg rhBMP-2. The presence of vancomycin changed the absorption patterns of endogenous proteins on the grafts, but did not appear to substantially compromise graft healing. CONCLUSIONS: The composite pHEMA-nHA-vancomycin preabsorbed with 3-µg rhBMP-2 promoted repair of 5 mm rat femoral segmental defects. With the sample sizes applied, vancomycin encapsulation did not appear to have a negative effect on bone healing. CLINICAL RELEVANCE: pHEMA-nHA-vancomycin preabsorbed with rhBMP-2 may be useful in the repair of critical-size long bone defects prone to infections.

Strengthening Quality Measurement to Predict Success for Total Knee Arthroplasty: Results from a Nationally Representative Total Knee Arthroplasty Cohort.

BACKGROUND: When performed well on appropriate patients, total knee arthroplasty (TKA) can dramatically improve quality of life. Patient-reported outcome measures (PROMs) are increasingly used to measure outcome following TKA. Accurate prediction of improvement in PROMs after TKA potentially plays an important role in judging the surgical quality of the health-care institutions as well as informing preoperative shared decision-making. Starting in 2027, the U.S. Centers for Medicare & Medicaid Services (CMS) will begin mandating PROM reporting to assess the quality of TKAs. METHODS: Using data from a national cohort of patients undergoing primary unilateral TKA, we developed an original model that closely followed a CMS-proposed measure to predict success, defined as achieving substantial clinical benefit, specifically at least a 20-point improvement on the Knee injury and Osteoarthritis Outcome Score, Joint Arthroplasty (KOOS, JR) at 1 year, and an enhanced model with just 1 additional predictor: the baseline KOOS, JR. We evaluated each model's performance using the area under the receiver operator characteristic curve (AUC) and the ratio of observed to expected (model-predicted) outcomes (O:E ratio). RESULTS: We studied 5,958 patients with a mean age of 67 years; 63% were women, 93% were White, and 87% were overweight or obese. Adding the baseline KOOS, JR improved the AUC from 0.58 to 0.73. Ninety-four percent of those in the top decile of predicted probability of success under the enhanced model achieved success, compared with 34% in its bottom decile. Analogous numbers for the original model were less discriminating: 77% compared with 57%. Only the enhanced model predicted success accurately across the spectrum of baseline scores. The findings were virtually identical when we replicated these analyses on only patients ≥65 years of age. CONCLUSIONS: Adding a baseline knee-specific PROM score to a quality measurement model in a nationally representative cohort dramatically improved its predictive power, eliminating ceiling and floor effects and mispredictions for readily identifiable patient subgroups. The enhanced model neither favors nor discourages care for those with greater knee dysfunction and requires no new data collection. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Integrating patient-reported outcomes into orthopaedic clinical practice: proof of concept from FORCE-TJR.

BACKGROUND: Good orthopaedic care requires a knowledge of the patient's history of musculoskeletal pain and associated limitations in daily function. Standardized measures of patient-reported outcomes (PROs) can provide this information. Integrating PROs into routine orthopaedic patient visits can provide key information to monitor changes in symptom severity over time, support shared clinical care decisions, and assess treatment effectiveness for quality initiatives and value-based reimbursement. WHERE ARE WE NOW?: Although standardized, validated PRO surveys are routinely used in clinical and comparative effectiveness research, they are not consistently or efficiently collected in clinical practice. WHERE DO WE NEED TO GO?: Ideally, PROs need to be collected directly from patients before their surgeon visit so the data are readily available to the surgeon and patient at the time of the office visit. In addition, PROs should be integrated in the electronic health record to monitor patient status over time. HOW DO WE GET THERE?: PRO integration in clinical practice requires minor modifications to the office flow, some additional staff to facilitate collection, and the technical infrastructure to score, process, and store the responses. We document successful office procedures for collecting PROs in one busy orthopaedic clinic and some suggested methods to extend this model to the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) consortium of 121 surgeons where the process is centralized and staff obtained consent to send the PRO directly to the patient's home. Both methods are options for the broader adoption of office-based PROs.

Incorporating patient-reported outcomes in total joint arthroplasty registries: challenges and opportunities.

BACKGROUND: Total joint arthroplasty (TJA) registries traditionally have focused on implant longevity and rates of revision surgery. Registries would benefit from the addition of standardized patient-reported outcomes (PROs) such as pain relief and improved physical function. However, PROs have not been routinely adopted, and their incorporation into TJA registries presents challenges. QUESTIONS/PURPOSES: We review current PRO use by existing national registries, challenges to integrating PROs in national registries, lessons from national registries that have integrated PROs, and suggestions to guide future adoption of PROs. METHODS: We conducted a literature search of papers addressing PRO use in national knee and hip arthroplasty registries, resulting in 15 articles. These publications were supplemented by discussions with thought leaders from international registries. WHERE ARE WE NOW?: Some national TJA registries are collecting PROs and valuable research is emerging. However, challenges exist, such as selecting suitable PROs, selection bias in countries without government-mandated participation for all hospitals, and challenges with missing data. WHERE DO WE NEED TO GO?: The ideal system will incorporate PROs into TJA registries. In so doing, it will be important to choose suitable PROs and develop innovative methods to collect PROs to ensure complete data and sustainability. HOW DO WE GET THERE?: New methods are required to meet the challenges related to registry design, logistics of PRO collection, and registry cost and sustainability. Modifications to the traditional hospital- and implant-centric design and new procedures to collect complete data from both patients and clinicians may be necessary. For instance, England and Wales, New Zealand, and Sweden developed methods to collect PROs after TJA directly from patients and a US TJA registry collects PROs as the primary outcome. Finally, to assure long-term sustainability, PRO data must be valuable to multiple stakeholders, including patients, clinicians, researchers, and policy makers.

pHEMA-nHA encapsulation and delivery of vancomycin and rhBMP-2 enhances its role as a bone graft substitute.

BACKGROUND: Bone grafts are widely used in orthopaedic procedures. Autografts are limited by donor site morbidity while allografts are known for considerable infection and failure rates. A synthetic composite bone graft substitute poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) was previously developed to stably press-fit in and functionally repair critical-sized rat femoral segmental defects when it was preabsorbed with a single low dose of 300 ng recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7). QUESTIONS/PURPOSES: To facilitate clinical translation of pHEMA-nHA as a synthetic structural bone graft substitute, we examined its ability to encapsulate and release rhBMP-2 and the antibiotic vancomycin. METHODS: We analyzed the compressive behavior and microstructure of pHEMA-nHA as a function of vancomycin incorporation doses using a dynamic mechanical analyzer and a scanning electron microscope. In vitro release of vancomycin was monitored by ultraviolet-visible spectroscopy. Release of rhBMP-2 from pHEMA-nHA-vancomycin was determined by ELISA. Bioactivity of the released vancomycin and rhBMP-2 was examined by bacterial inhibition and osteogenic transdifferentiation capabilities in cell culture, respectively. RESULTS: Up to 4.8 wt% of vancomycin was incorporated into pHEMA-nHA without compromising its structural integrity and compressive modulus. Encapsulated vancomycin was released in a dose-dependent and sustained manner in phosphate-buffered saline over 2 weeks, and the released vancomycin inhibited Escherichia coli culture. The pHEMA-nHA-vancomycin composite released preabsorbed rhBMP-2 in a sustained manner over 8 days and locally induced osteogenic transdifferentiation of C2C12 cells in culture. CONCLUSIONS: pHEMA-nHA can encapsulate and deliver vancomycin and rhBMP-2 in a sustained and localized manner with reduced loading doses. CLINICAL RELEVANCE: The elasticity, osteoconductivity, and rhBMP-2/vancomycin delivery characteristics of pHEMA-nHA may benefit orthopaedic reconstructions or fusions with enhanced safety and efficiency and reduced infection risk.

Modulating On-Demand Release of Vancomycin from Implant Coatings via Chemical Modification of a Micrococcal Nuclease-Sensitive Oligonucleotide Linker.

Periprosthetic infections are one of the most serious complications in orthopedic surgeries, and those caused by Staphylococcus aureus (S. aureus) are particularly hard to treat due to their tendency to form biofilms on implants and their notorious ability to invade the surrounding bones. The existing prophylactic local antibiotic deliveries involve excessive drug loading doses that could risk the development of drug resistance strains. Utilizing an oligonucleotide linker sensitive to micrococcal nuclease (MN) cleavage, we previously developed an implant coating capable of releasing covalently tethered vancomycin, triggered by S. aureus-secreted MN, to prevent periprosthetic infections in the mouse intramedullary (IM) canal. To further engineer this exciting platform to meet broader clinical needs, here, we chemically modified the oligonucleotide linker by a combination of 2'-O-methylation and phosphorothioate modification to achieve additional modulation of its stability/sensitivity to MN and the kinetics of MN-triggered on-demand release. We found that when all phosphodiester bonds within the oligonucleotide linker 5'-carboxy-mCmGTTmCmG-3-acrydite, except for the one between TT, were replaced by phosphorothioate, the oligonucleotide (6PS) stability significantly increased and enabled the most sustained release of tethered vancomycin from the coating. By contrast, when only the peripheral phosphodiester bonds at the 5'- and 3'-ends were replaced by phosphorothioate, the resulting oligonucleotide (2PS) linker was cleaved by MN more rapidly than that without any PS modifications (0PS). Using a rat femoral canal periprosthetic infection model where 1000 CFU S. aureus was inoculated at the time of IM pin insertion, we showed that the prophylactic implant coating containing either 0PS- or 2PS-modified oligonucleotide linker effectively eradicated the bacteria by enabling the rapid on-demand release of vancomycin. No bacteria were detected from the explanted pins, and no signs of cortical bone changes were detected in these treatment groups throughout the 3 month follow-ups. With an antibiotic tethering dose significantly lower than conventional antibiotic-bearing bone cements, these coatings also exhibited excellent biocompatibility. These chemically modified oligonucleotides could help tailor prophylactic anti-infective coating strategies to meet a range of clinical challenges where the risks for S. aureus prosthetic infections range from transient to long-lasting.

Challenging Diagnosis of Stickler Syndrome in a Patient with Premature Osteoarthritis: A Case Report.

CASE: A 53-year-old male patient, subsequently diagnosed with type I Stickler syndrome, presented with severe premature osteoarthritis associated with bilateral hip dysplasia and knee epiphyseal dysplasia. Despite the presence of the typical manifestations of orofacial defects, hearing, ocular, and musculoskeletal abnormalities, the patient had never been diagnosed with the syndrome. CONCLUSION: Stickler syndrome can present with a wide spectrum of musculoskeletal abnormalities without previous diagnosis. It is often underrecognized if the manifestations of other systems are not appreciated. Stickler syndrome should be considered in the differential diagnosis of patients with unexplained musculoskeletal abnormality particularly in the presence of other system manifestations.