Causal relationships between pain, medical treatments, and knee osteoarthritis: A graphical causal model to guide analyses.

OBJECTIVE: Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA). METHODS: We identified 2 post-randomization events likely to impact accurate assessment of pain outcomes beyond 5 years in trial participants: loss to follow-up and total knee replacement (TKR). We conducted literature searches for covariates related to pain and TKR in individuals with knee OA and combined these with expert input. We synthesized the evidence into graphical models. RESULTS: We identified 94 potential covariates potentially related to pain and/or TKR among individuals with knee OA. Of these, 46 were identified in the literature review and 48 by expert panelists. We determined that adjustment for 50 covariates may be required to estimate the long-term effects of knee OA treatments on pain. CONCLUSION: We present a process for combining literature reviews with expert input to synthesize existing knowledge and improve covariate selection. We apply this process to the long-term follow-up of a randomized trial and show that expert input provides additional information not obtainable from literature reviews alone.

A consensus-based process identifying physical therapy and exercise treatments for patients with degenerative meniscal tears and knee OA: the TeMPO physical therapy interventions and home exercise program.

BACKGROUND: Knee osteoarthritis (OA) is prevalent and often associated with meniscal tear. Physical therapy (PT) and exercise regimens are often used to treat OA or meniscal tear, but, to date, few programs have been designed specifically for conservative treatment of meniscal tear with concomitant knee OA. Clinical care and research would be enhanced by a standardized, evidence-based, conservative treatment program and the ability to study the effects of the contextual factors associated with interventions for patients with painful, degenerative meniscal tears in the setting of OA. This paper describes the process of developing both a PT intervention and a home exercise program for a randomized controlled clinical trial that will compare the effectiveness of these interventions for patients with knee pain, meniscal tear and concomitant OA. METHODS: This paper describes the process utilized by an interdisciplinary team of physical therapists, physicians, and researchers to develop and refine a standardized in-clinic PT intervention, and a standardized home exercise program to be carried out without PT supervision. The process was guided in part by Medical Research Council guidance on intervention development. RESULTS: The investigators achieved agreement on an in-clinic PT intervention that included manual therapy, stretching, strengthening, and neuromuscular functional training addressing major impairments in range of motion, musculotendinous length, muscle strength and neuromotor control in the major muscle groups associated with improving knee function. The investigators additionally achieved agreement on a progressive, protocol-based home exercise program (HEP) that addressed the same major muscle groups. The HEP was designed to allow patients to perform and progress the exercises without PT supervision, utilizing minimal equipment and a variety of methods for instruction. DISCUSSION: This multi-faceted in-clinic PT program and standardized HEP provide templates for in-clinic and home-based care for patients with symptomatic degenerative meniscal tear and concomitant OA. These interventions will be tested as part of the Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 on February 14, 2017. TeMPO was also approved by the Institutional Review Board at Partners HealthCare/Brigham and Women's Hospital.

Activity Impairment and Work Productivity Loss After Total Knee Arthroplasty: A Prospective Study.

BACKGROUND: Total knee arthroplasty (TKA) is increasingly performed among working-aged individuals, highlighting the importance of work-related outcomes. Therefore, the aim is to examine the extent of both activity impairment outside work and work productivity (absenteeism, presenteeism, at-work productivity loss) at 6 and 24 months post-TKA surgery. Additionally, associated risk factors with these outcomes were evaluated. METHODS: This analysis included 183 patients <70 years undergoing TKA who completed questionnaires pre-operatively and during follow-up. Outcomes were derived from the Work Productivity and Activity Impairment questionnaire and included activity impairment, absenteeism (sick leave), presenteeism (reduced work performance), and at-work productivity loss (overall work productivity loss). All outcomes were scaled 0%-100%, with higher percentages indicating higher impairments. Covariates included age, gender, education, pain catastrophizing, pain, function, psychological distress, and knee-related and health-related quality of life. Linear and logistic regression was used to assess associations between covariates and Work Productivity and Activity Impairment scores at follow-up. RESULTS: At 6 months, the mean activity impairment was 22.8% (standard deviation [SD] 23.5) dropping to 17.1% (23.1) by 24 months. Among workers, presenteeism was 18.4% (24.6) and at-work productivity loss was 20.8% (26.1). Both dropped significantly by 24 months to 14.2% (22.4) and 12.9% (20.9), respectively. Absenteeism levels were low at both time points. Pain catastrophizing was associated with all outcomes. CONCLUSION: This study showed that activity impairment and work productivity loss are common following TKA, decreased significantly over time, but still existed 2 years post-operatively. Those reporting high levels of pain catastrophizing may benefit from targeted rehabilitation guidance to reduce and possibly prevent activity impairment and work productivity loss.

The TeMPO trial (treatment of meniscal tears in osteoarthritis): rationale and design features for a four arm randomized controlled clinical trial.

BACKGROUND: Meniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects. METHODS: The Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs. DISCUSSION: The goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 . on February 14, 2017.

Predictors of Exercise Adherence in Patients With Meniscal Tear and Osteoarthritis.

OBJECTIVE: To identify predictors of poor exercise adherence in patients with osteoarthritis (OA) and meniscal tear. DESIGN: Secondary analysis of data gathered over the first 12 weeks in the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial, a multicenter, randomized controlled trial. SETTING: Seven referral centers. PARTICIPANTS: Most of the patients in the MeTeOR trial (N=325 of 351) were included in the analysis, each of whom was aged ≥45 years and had a meniscal tear and osteoarthritic changes on imaging studies; 26 were excluded because of missing data from which to derive the primary outcome variable. INTERVENTIONS: All patients received a structured, supervised exercise program focused on strengthening, along with prescribed home exercises; half were randomly assigned to also receive arthroscopic partial meniscectomy. MAIN OUTCOME MEASURE: Poor exercise adherence through 12 weeks, defined as performing <50% of prescribed exercise. RESULTS: Thirty-eight percent of the MeTeOR cohort showed poor exercise adherence. In the multivariate model, adjusting for treatment group, those who earned ≤$29,000 per year had 1.64 times the risk of nonadherence (95% confidence interval [CI], 1.10-2.43) than those who earned >$100,000 per year; and those without baseline pain with pivoting and twisting had 1.60 times greater risk of nonadherence than those with these symptoms (95% CI, 1.14-2.25). CONCLUSIONS: Low income was associated with poor exercise adherence among patients aged ≥45 years with OA and a meniscal tear, as was absence of pain with pivoting and twisting. Our findings highlight the need for further research into exercise adherence and for interventions to enhance adherence among those with low incomes.

Association between activity limitations and pain in patients scheduled for total knee arthroplasty.

BACKGROUND: Historically, persons scheduled for total knee arthroplasty (TKA) have reported severe pain with low demand activities such as walking, but recent data suggests that TKA recipients may have less preoperative pain. Little is known about people who elect TKA with low levels of preoperative pain. To better understand current TKA utilization, we evaluated the association between preoperative pain and difficulty performing high demand activities, such as kneeling and squatting, among TKA recipients. METHODS: We used baseline data from a randomized control trial designed to improve physical activity following TKA. Prior to TKA, participants were categorized according to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scores: Low (0-25), Medium (26-40), and High (41-100). Within each group, limitations in both low demand and high demand activities were assessed. RESULTS: The sample consisted of 202 persons with a mean age of 65 (SD 8) years; 21 %, 34 %, and 45 % were categorized in the Low, Medium, and High Pain groups, respectively. Of the Low Pain group, 60 % reported at least one of the following functional limitations: limited flexion, limp, limited walking distance, and limitations in work or housework. While only 12 % of the Low Pain group reported at least moderate pain with walking on a flat surface, nearly all endorsed at least moderate difficulty with squatting and kneeling. CONCLUSIONS: A substantial number of persons scheduled for TKA report Low WOMAC Pain (≤25) prior to surgery. Persons with Low WOMAC Pain scheduled for TKA frequently report substantial difficulty with high demand activities such as kneeling and squatting. Studies of TKA appropriateness and effectiveness for patients with low WOMAC Pain should include measures of these activities. TRIAL REGISTRATION: Identifier NCT01970631 ; Registered 23 October 2013.

Is there an association between whole-body pain with osteoarthritis-related knee pain, pain catastrophizing, and mental health?

BACKGROUND: Greater levels of self-reported pain, pain catastrophizing, and depression have been shown to be associated with persistent pain and functional limitation after surgeries such as TKA. It would be useful for clinicians to be able to measure these factors efficiently. QUESTIONS/PURPOSES: We asked: (1) What is the association of whole-body pain with osteoarthritis (OA)-related knee pain, function, pain catastrophizing, and mental health? (2) What is the sensitivity and specificity for different cutoffs for body pain diagram region categories in relation to pain catastrophizing? METHODS: Patients (n = 267) with knee OA undergoing elective TKA at one academic center and two community orthopaedic centers were enrolled before surgery in a prospective cohort study. Questionnaires included the WOMAC Pain and Function Scales, Pain Catastrophizing Scale (PCS), Mental Health Inventory-5 (MHI-5), and a pain body diagram. The diagram documents pain in 19 anatomic areas. Based on the distribution of the anatomic areas, we established six different body regions. Our analyses excluded the index (surgically treated) knee. Linear regression was used to evaluate the association between the total number of nonindex painful sites on the whole-body pain diagram and measures of OA-related pain and function, mental health, and pain catastrophizing. Generalized linear regression was used to evaluate the association between the number of painful nonindex body regions (categorized as 0; 1-2; or 3-6) with our measures of interest. All models were adjusted for age, sex, and number of comorbid conditions. The cohort included 63% females and the mean age was 66 years (SD, 9 years). With removal of the index knee, the median pain diagram score was 2 (25(th), 75(th) percentiles, 1, 4) with a range of 0 to 15. The median number of painful body regions was 2 (25(th), 75(th) percentiles, 1, 3). RESULTS: After adjusting for age, sex, and number of comorbid conditions, we found modest associations between painful body region categories and mean scores for WOMAC physical function (r = 0.22, p < 0.001), WOMAC pain (r = 0.20, p = 0.001), MHI-5 (r = -0.31, p < 0.001), and PCS (r = 0.27, p < 0.001). A nonindex body pain region score greater than 0 had 100% (95% CI, 75%-100%) sensitivity for a pain catastrophizing score greater than 30 but a specificity of just 23% (95% CI, 18%-29%) . A score of 3 or greater had greater specificity (73%; 95% CI, 66%-79%) but lower sensitivity (53%; 95% CI, 27%-78%). CONCLUSIONS: We found modest associations between the number of painful sites on a whole-body pain diagram and the number of painful body regions and measures of OA-related pain, function, pain catastrophizing, and mental health. Patients with higher self-reported body pain region scores might benefit from further evaluation for depression and pain catastrophizing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Outcomes of small coronary artery stenting with bare-metal stents versus drug-eluting stents: results from the NHLBI Dynamic Registry.

OBJECTIVES: Examine 1-year outcomes of patients with small coronary arteries in the National Heart, Lung, and Blood Institute Dynamic Registry (NHLBI) undergoing drug-eluting stent (DES) vs. bare-metal stent (BMS) placement. BACKGROUND: While randomized trials of DES vs. BMS demonstrate reduced target vessel revascularization, it is unclear whether similar outcomes are seen in unselected patients after percutaneous coronary intervention (PCI) for small coronary arteries. METHODS: Utilizing patients from the NHLBI Registry Waves 1-3 for BMS (1997-2002) and Waves 4-5 for DES (2004 and 2006), demographic, angiographic, in-hospital, and 1-year outcome data of patients with small coronary arteries treated with BMS (n = 686) vs. DES (n = 669) were evaluated. Small coronary artery was defined as 2.50-3.00 mm in diameter. RESULTS: Compared to BMS-treated patients, the mean lesion length of treated lesions was longer in the DES treated group (16.7 vs. 13.1 mm, P < 0.001) and the mean reference vessel size of attempted lesions was smaller (2.6 vs. 2.7 mm, P < 0.001). Adjusted analyses of 1-year outcomes revealed that DES patients were at lower risk to undergo coronary artery bypass graft surgery (Hazard Ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), repeat PCI (HR 0.53, 95% CI 0.35-0.82, P = 0.004), and experience the combined major adverse cardiovascular event rate (HR 0.59, 95% CI 0.42-0.83, P = 0.002). There was no difference in the risk of death and myocardial infarction (MI) (HR 0.78, 95% CI 0.46-1.35, P = 0.38). CONCLUSIONS: In this real-world registry, patients with small coronary arteries treated with DES had significantly lower rates of repeat revascularization and major adverse cardiovascular events at 1 year compared to patients treated with BMS, with no increase in the risk of death and MI. These data confirm the efficacy and safety of DES over BMS in the treatment of small coronary arteries in routine clinical practice.

Comparison of drug-eluting and bare metal stents in large coronary arteries: findings from the NHLBI dynamic registry.

OBJECTIVES: This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. BACKGROUND: Randomized trials have demonstrated that DES reduce the risk of target vessel revascularization (TVR) compared to BMS. This benefit is less pronounced as artery diameter increases. Whether DES are superior to BMS for larger coronary arteries in the setting of routine clinical practice is unknown. METHODS: We analyzed data from 869 patients undergoing de novo lesion PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI Dynamic Registry according to whether they were treated with DES or BMS. Patients were followed for 3 years for the occurrence of cardiovascular events. RESULTS: At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI 0.93-3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52-2.49, P = 0.75) and for mortality 0.89 (95%CI 0.49-1.62, P = 0.71). CONCLUSIONS: In our study of the unrestricted use of DES for patients with lesions in larger diameter coronary arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do not support the preferred use of DES over BMS for patients with lesions located in arteries >3.5 mm. It is unknown whether secondary generation DES can offer better outcome compared to BMS in large coronary vessels. Further study on this issue is warranted.

Factors Associated With Diagnostic Delay in Axial Spondyloarthritis: Impact of Clinical Factors and Social Vulnerability.

OBJECTIVE: Patients with axial spondyloarthritis (axSpA) often experience significant delay between symptom onset and diagnosis for reasons that are incompletely understood. We investigated associations between demographic, medical, and socioeconomic factors and axSpA diagnostic delay. METHODS: We identified patients meeting modified New York criteria for ankylosing spondylitis (AS) or 2009 Assessment of Spondyloarthritis International Society criteria for axSpA in the Mass General Brigham health care system between December 1990 and October 2021. We determined the duration of diagnostic delay, defined as the duration of back pain symptoms reported at diagnosis, as well as disease manifestations and specialty care prior to diagnosis from the electronic health record. We obtained each patient's Social Vulnerability Index (SVI) by mapping their address to the US Centers for Disease Control SVI Atlas. We examined associations among disease manifestations, SVI, and diagnostic delay using ordinal logistic regression. RESULTS: Among 554 patients with axSpA who had a median diagnostic delay of 3.8 years (interquartile range 1.1-10), peripheral arthritis (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.93) and older age at symptom onset (OR 0.83, 95% CI 0.78-0.88 per five years) were associated with shorter delay. AS at diagnosis (OR 1.85, 95% CI 1.30-2.63), a history of uveitis prior to diagnosis (OR 2.77, 95% CI 1.73-4.52), and higher social vulnerability (defined as national SVI 80th to 99th percentiles; OR 1.99, 95% CI 1.06-3.84) were associated with longer diagnostic delay. CONCLUSION: Older age at back pain onset and peripheral arthritis were associated with shorter delay, whereas uveitis was associated with longer diagnostic delay. Patients with higher socioeconomic vulnerability had longer diagnostic delay independent of clinical factors.

Frailty Is More Predictive of Mortality than Age in Patients With Hip Fractures.

OBJECTIVES: To investigate the association between the Comprehensive Geriatric Assessment-based Frailty Index and adverse outcomes in older adult patients undergoing hip fracture surgery. DESIGN: Retrospective cohort study. SETTING: Academic Level 1 Trauma Center. PATIENTS: All patients aged 65 or older who underwent surgical repair of a hip fracture between May 2018 and August 2020 were identified through institutional database review. OUTCOME MEASURES AND COMPARISONS: Data including demographics, FI, injury presentation, and hospital course were collected. Patients were grouped by FI as nonfrail (FI < 0.21), frail (0.21 ≤ FI < 0.45), and severely frail (FI > 0.45). Adverse outcomes of these groups were compared using Kaplan Meier survival analysis. Risk factors for 1-year rehospitalization and 2-year mortality were evaluated using Cox hazard regression. RESULTS: Three hundred sixteen patients were included, with 62 nonfrail, 185 frail, and 69 severely frail patients. The total population was on average 83.8 years old, predominantly white (88.0%), and majority female (69.9%) with an average FI of 0.33 (SD: 0.14). The nonfrail cohort was on average 78.8 years old, 93.6% white, and 80.7% female; the frail cohort was on average 84.5 years old, 92.4% white, and 71.9% female; and the severely frail cohort was on average 86.4 years old, 71.0% white, and 55.1% female. Rate of 1-year readmission increased with frailty level, with a rate of 38% in nonfrail patients, 55.6% in frail patients, and 74.2% in severely frail patients (P = 0.001). The same pattern was seen in 2-year mortality rates, with a rate of 2.8% in nonfrail patients, 36.7% in frail patients, and 77.5% in severely frail patients (P < 0.0001). Being classified as frail or severely frail exhibited greater association with mortality within 2 years than age, with hazard ratio of 17.81 for frail patients and 56.81 for severely frail patients compared with 1.19 per 5 years of age. CONCLUSIONS: Increased frailty as measured by the Frailty Index is significantly associated with increased 2-year mortality and 1-year hospital readmission rates after hip fracture surgery. Degree of frailty predicts mortality more strongly than age alone. Assessing frailty with the Frailty Index can identify higher-risk surgical candidates, facilitate clinical decision making, and guide discussions about goals of care with family members, surgeons, and geriatricians. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Responsiveness of Subjective and Objective Measures of Pain and Function Following Operative Interventions for Musculoskeletal Conditions: A Narrative Review.

OBJECTIVE: Musculoskeletal (MSK) disorders affect ~50% of US adults and 75% of those over the age of 65, representing a sizable economic and disability burden. Outcome measures, both objective and subjective, help clinicians and investigators determine whether interventions to treat MSK conditions are effective. This narrative review qualitatively compared the responsiveness of different types of outcome measures, a key measurement characteristic that assesses an outcome measure's ability to detect change in patient status. METHODS: We evaluated elective orthopedic interventions as a model for assessing responsiveness because the great majority of patients improves following surgery. We searched for articles reporting responsiveness (quantified as effect size [ES]) of subjective and objective outcome measures after orthopedic surgery and included 16 articles reporting 17 interventions in this review. RESULTS: In 14 of 17 interventions, subjective function measures had an ES 10% greater than that of objective function measures. Two reported a difference in ES of <10%. The sole intervention that demonstrated higher ES of objective function used a composite measure. Sixteen interventions reported measures of subjective pain and/or mixed measures and subjective function. In nine interventions, subjective pain had a higher ES than subjective function by >10%, in three, subjective function had a higher ES than subjective pain by >10%, and in the remaining four, the difference between pain and function was <10%. CONCLUSION: These findings reinforce the clinical observation that subjective pain generally changes more than function following elective orthopedic surgery. They also suggest that subjective function measures are more responsive than objective function measures, and composite scores may be more responsive than individual performance tests.

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale.

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) â€‹≥ â€‹30 â€‹kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA. Trial registration: ClinicalTrials.gov Identifier: NCT05946044.

An approach to virtual clinical trial site visits: Lessons from the MeTeOR trial.

Objective: To provide a framework for conducting clinical trial site visits virtually over videoconference, and to report on our experience doing so during the twelve-year follow-up of the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. Design: Using published FDA guidance and prior literature, we created a structure for virtual site visits that prioritized monitoring for protocol compliance, safety, and data integrity. We conducted site visits in three stages: preparation for the visit, the virtual meeting itself, and follow-up. The preparation phase involved a review of relevant site-specific documents and a written report on the findings prior to the visit. The virtual visit itself was focused on any questions the site staff had about the pre-visit report, observing a mock study visit, touring physical spaces, and understanding the site staff's work environment. In the follow-up phase, we wrote a post-visit report summarizing the discussion during the visit and feedback given by the coordinating site. Results: We found that the virtual site visits conducted as part of the MeTeOR trial follow-up ran smoothly. Although we could not directly compare in-person and virtual site visits, site staff unanimously appreciated the efficiency and effectiveness of the virtual site visits. We noted that displaying physical workspaces over videoconferencing was difficult, and a notable drawback to this method. Conclusions: To our knowledge, this is the first published framework for conducting virtual clinical trial site visits. Conducting these visits virtually confer several advantages in terms of time, money, and efficiency.

Assessment of Residual Pain and Dissatisfaction in Total Knee Arthroplasty: Methods Matter.

Background: Residual pain after total knee arthroplasty (TKA) refers to knee pain after 3 to 6 months postoperatively. The estimates of the proportion of patients who experience residual pain after TKA vary widely. We hypothesized that the variation may stem from the range of methods used to assess residual pain. We analyzed data from 2 prospective studies to assess the proportion of subjects with residual pain as defined by several commonly used metrics and to examine the association of residual pain defined by each metric with participant dissatisfaction. Methods: We combined participant data from 2 prospective studies of TKA outcomes from subjects recruited between 2011 and 2014. Residual pain was defined using a range of metrics based on the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score (0 to 100, in which 100 indicates worst), including the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). We also examined combinations of MCID and PASS cutoffs. Subjects self-reported dissatisfaction following TKA, and we defined dissatisfied as somewhat or very dissatisfied at 12 months. We calculated the proportion of participants with residual pain, as defined by each metric, who reported dissatisfaction. We examined the association of each metric with dissatisfaction by calculating the sensitivity, specificity, positive predictive value, and Youden index. Results: We analyzed data from 417 subjects with a mean age (and standard deviation) of 66.3 ± 8.3 years. Twenty-six participants (6.2%) were dissatisfied. The proportion of participants defined as having residual pain according to the various metrics ranged from 5.5% to >50%. The composite metric Improvement in WOMAC pain score ≥20 points or final WOMAC pain score ≤25 had the highest positive predictive value for identifying dissatisfied subjects (0.54 [95% confidence interval, 0.35 to 0.71]). No metric had a Youden index of ≥50%. Conclusions: Different metrics provided a wide range of estimates of residual pain following TKA. No estimate was both sensitive and specific for dissatisfaction in patients who underwent TKA, underscoring that measures of residual pain should be defined explicitly in reports of TKA outcomes. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cost-Effectiveness of Surgical Weight-Loss Interventions for Patients With Knee Osteoarthritis and Class III Obesity.

OBJECTIVE: Class III obesity (body mass index [BMI] ≥40 kg/m2 ) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m2 , our objective was to establish the value of Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m2 . METHODS: We used the Osteoarthritis Policy model to assess long-term clinical benefits, costs, and cost-effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. RESULTS: The usual care + RYGB strategy increased the quality-adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m2 , usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost-effective in 70% and 30% of iterations, respectively. CONCLUSION: RYGB offers good value among knee OA patients with BMI ≥40 kg/m2 , while LSG may provide good value among those with BMI between 35 and 41 kg/m2 .

Cost-Effectiveness of Weight-Loss Interventions Prior to Total Knee Replacement for Patients With Class III Obesity.

OBJECTIVE: Class III obesity (body mass index >40 kg/m2 ) is associated with higher complications following total knee replacement (TKR), and weight loss is recommended. We aimed to establish the cost-effectiveness of Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and lifestyle nonsurgical weight loss (LNSWL) interventions in knee osteoarthritis patients with class III obesity considering TKR. METHODS: Using the Osteoarthritis Policy model and data from published literature to derive model inputs for RYGB, LSG, LNSWL, and TKR, we assessed the long-term clinical benefits, costs, and cost-effectiveness of weight-loss interventions for patients with class III obesity considering TKR. We assessed the following strategies with a health care sector perspective: 1) no weight loss/no TKR, 2) immediate TKR, 3) LNSWL, 4) LSG, and 5) RYGB. Each weight-loss strategy was followed by annual TKR reevaluation. Primary outcomes were cost, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs), discounted at 3% per year. We conducted deterministic and probabilistic sensitivity analyses to examine the robustness of conclusions to input uncertainty. RESULTS: LSG increased QALE by 1.64 quality-adjusted life-years (QALYs) and lifetime medical costs by $17,347 compared to no intervention, leading to an ICER of $10,600/QALY. RYGB increased QALE by 0.22 and costs by $4,607 beyond LSG, resulting in an ICER of $20,500/QALY. Relative to immediate TKR, LSG and RYGB delayed and decreased TKR utilization. In the probabilistic sensitivity analysis, RYGB was cost-effective in 67% of iterations at a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: For patients with class III obesity considering TKR, RYGB provides good value while immediate TKR without weight loss is not economically efficient.

Radiographic Changes Five Years After Treatment of Meniscal Tear and Osteoarthritic Changes.

OBJECTIVE: Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not respond. Prior studies suggest APM may be associated with greater progression of radiographic changes. METHODS: We assessed changes between baseline and 60 months in the Kellgren-Lawrence (KL) grade and OARSI radiographic score (including subscores for joint space narrowing and osteophytes) in subjects aged 45-85 years enrolled into a seven-center randomized trial comparing outcomes of APM with PT for meniscal tear, osteoarthritis changes, and knee pain. The primary analysis classified subjects according to treatment received. To balance APM and PT groups, we developed a propensity score and used inverse probability weighting (IPW). We imputed a 60-month change in the OARSI score for subjects who underwent total knee replacement (TKR). In a sensitivity analysis, we classified subjects by randomization group. RESULTS: We analyzed data from 142 subjects (100 APM, 42 PT). The mean ± SD weighted baseline OARSI radiographic score was 3.8 ± 3.5 in the APM group and 4.0 ± 4.9 in the PT group. OARSI scores increased by a mean of 4.1 (95% confidence interval [95% CI] 3.5-4.7) in the APM group and 2.4 (95% CI 1.7-3.2) in the PT group (P < 0.001) due to changes in the osteophyte component. We did not observe statistically significant differences in the KL grade. Sensitivity analyses yielded similar findings to the primary analysis. CONCLUSION: Subjects treated with APM had greater progression in the OARSI score because of osteophyte progression but not in the KL grade. The clinical implications of these findings require investigation.

Direct stenting compared to balloon predilation in drug-eluting stents: one-year outcomes from the DEScover Registry.

OBJECTIVES: We sought to examine the determinants and outcomes of direct stenting (DS) compared to predilation with drug-eluting stents (DES). BACKGROUND: Limited data suggest that DS with DES is feasible and may reduce restenosis compared to predilation. Whether DS improves clinical outcomes in unselected patients treated with DES is unknown. METHODS: DEScover is a prospective, multicenter, observational study of percutaneous coronary intervention that enrolled patients in 2005. The analysis cohort included 4,210 patients who received a DES and had a single lesion treated with DS (n = 1,651) or predilation (n = 2,559) at the discretion of the operator. Multivariable analysis was performed for 1-year outcomes. RESULTS: DS was performed in 39.2% of patients. The direct stent patients were younger, less often male, and had a lesser extent of CAD. DS was performed less often in patients presenting with an acute myocardial infarction (MI) and more often in stable angina and elective procedures. Lesion characteristics differed with DS performed less often for calcified lesions, high-grade stenoses (>90%), and bifurcation lesions. Lesion postdilation was less common in direct stent patients (42.1% vs. 50.7%, P = 0.0001). Complete procedural success was similar (99.8% vs. predilation 99.7%, P = 0.46). At 1 year, there was no difference in the adjusted hazard ratios of death (0.67, 0.44-1.04, P = 0.08), MI (1.05, 0.66-1.67, P = 0.83), stent thrombosis (0.38, 0.13-1.14, P = 0.08), TLR (0.75, 0.48-1.17, P = 0.21), TVR (0.89, 0.64-1.23, P = 0.47), and major adverse coronary event (0.88, 0.71-1.09, P = 0.24). CONCLUSIONS: DS with DES is commonly performed in clinical practice and results in similar long-term outcomes as predilation.

Objective performance tests assess aspects of function not captured by self-report in knee osteoarthritis.

Objective: Knee osteoarthritis (OA) can substantially limit function, which can be assessed both objectively and subjectively. We examined whether objective performance tests are associated with self-reported function. Methods: We analyzed baseline data from the Osteoarthritis Registry of Biomarker and Imaging Trajectories (ORBIT) of participants ≥40 years old with symptomatic and radiographic knee OA. Subjects completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Activities of Daily Living (ADL) scales and other assessments of pain and comorbidity. Subjects performed the timed single leg balance test (SLB), 30-s sit-to-stand (30s STS), Timed-Up-and-Go (TUG), and 40-m fast paced walk (40 â€‹m Walk). We used Pearson correlation coefficients to examine associations between performance and KOOS subscales. We adjusted for potential confounders using partial correlations. Results: We enrolled 101 subjects (mean age 63.7 (standard deviation (SD) 10.1), mean BMI 30.0 (SD 5.6), and 63% female). The mean (SD) values for the performance tests were: SLB 20.1 (18.9) seconds, 30s STS 11.7 (4.6) stands, TUG 9.4 (2.3) seconds, and 40 â€‹m Walk 27.6 (6.5) seconds. Correlations between performance tests and self-report measures did not exceed 0.39, with the absolute value of correlations between KOOS ADL and performance measures ranging from 0.24 to 0.39. Adjusted partial correlations were largely similar to the crude correlations. Conclusions: Self-reported function in persons with knee OA had weak to modest correlations with objective function. Objective performance tests capture elements of physical function that self-report data do not and point to the potential value of including objective measures of functional status in OA trials.