Patient-reported Quality of Life Before and After Total Knee Arthroplasty: A Prospective Multicentre Cohort Study

Background: To identify patients’ self-reported health-related quality of life (HRQoL) before and after total knee arthroplasty (TKA) and determine factors contributing to any heterogeneity in HRQoL. Methods: This prospective multicentre study included 404 patients with knee osteoarthritis who underwent TKA between 1 April and 30 December 2019 and in whom HRQoL was assessed preoperatively and at 7 days and 1, 3, and 6 months postoperatively. Sociodemographic characteristics were assessed using a general information questionnaire; disability, using the Knee Injury and Osteoarthritis Outcome Score; pain, using the visual analogue scale (VAS) score; and HRQoL, using the European Quality of Life Five Dimension Five Level (EQ-5D-5L) score. Potential heterogeneity and factors inuencing longitudinal changes in HRQoL were analysed using a growth mixture model. Results: The mean EQ-5D-5L score improved from 0.69 preoperatively to 0.90 at 6 months postoperatively. Two types of longitudinal heterogeneity were identied: (1) a group of patients with a small and slow improvement in HRQoL and (2) a group of patients who showed marked and rapid improvement in HRQoL. The main characteristics of the latter group were a monthly family income >2000 yuan, exercising for approximately 30 min daily, and better knee function at baseline. Baseline knee function and change in knee function were signicantly associated with the percentage change in HRQoL. Conclusions: HRQoL improved considerably after TKA. However, there was some heterogeneity in the changes in HRQoL depending on certain patient characteristics. Targeted interventions should focus on these differences to optimise the outcomes of TKA.


Background
Osteoarthritis is a common chronic musculoskeletal disease that affects nearly 400 million people worldwide and imposes a heavy socioeconomic burden on individuals and health care systems in many countries (1)(2)(3). Knee osteoarthritis (KOA) is present in 86.8% of osteoarthritis cases and is the main cause of knee pain (2)(3)(4). It is characterised by osteophyte formation and destruction of the articular cartilage of the knee. Patients with KOA often have reduced self-care ability and even disability due to joint pain, stiffness, and limited activity, which has an increasingly severe impact on their quality of life and leads to a wide range of social problems over time (3).
The prevalence of KOA in the Chinese population over 40 years of age is reported to be 17.0%, affecting 12.3% of men and 22.2% of women, and both these gures are higher than the world average values (5).
Furthermore, the prevalence of younger patients with KOA is increasing, and it is projected that the proportion of the population over the age of 45 years with a diagnosis of KOA will increase from 13.8- 15.7% by 2032 (6, 7). This degenerative disease adversely affects the health-related quality of life (HRQoL) of middle-aged and older patients and represents a substantial burden of disease in China.
Total knee arthroplasty (TKA) is the most effective treatment for end-stage KOA (8-11) and has been performed for more than 40 years (12,13). Previous studies have shown that 80-85% of patients with KOA have good outcomes after TKA (14)(15)(16). However, several studies have reported that not all patients are satis ed with the outcome after surgery, with 15-20% of patients reporting ongoing pain, poor joint function, postoperative infection, or complications, including a need for revision surgery (17).
Previous studies of TKA have focused primarily on the clinical effectiveness of the surgery and on risk factors (18, 19), costs versus bene ts of surgery (20), or the safety and e cacy of postoperative rehabilitation (21). Although some studies have investigated the HRQoL of patients after TKA (22,23), the factors affecting this change are not clear.
Therefore, we conducted this cohort study in Guangzhou, the largest city in southern China, to assess the self-reported HRQoL trajectories of patients with KOA before and after TKA and to identify the factors contributing to any differences in these trajectories.

Study design and participants
This prospective observational study enrolled patients who underwent TKA at four tertiary hospitals in four districts in Guangzhou, China, between 1 April 2019 and 30 December 2019. The following inclusion criteria were applied: 1) diagnosis of KOA based on the 2018 clinical guidelines for the diagnosis of osteoarthritis in China (24); 2) rst TKA procedure; 3) willingness and ability to complete questionnaires; and 4) completion of at least three of ve follow-up questionnaires. Patients with a psychiatric disorder, those with another serious disease, and those who were not independently self-caring were excluded. Questionnaires were distributed to patients by the investigators and medical students in the same year of training at the ve assessment points. In total, 404 of 520 patients with KOA screened at baseline met the study inclusion criteria and attended at least three follow-up visits. The screening process and follow-up of patients throughout the study are shown in Fig. 1.
This study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement for the reporting of observational studies.

General information questionnaire
Sociodemographic characteristics were obtained from a questionnaire adapted from the General Information Questionnaire developed by the International Consortium for Health Outcomes Measurement for KOA. Information collected included sex, age, marital status, education level, weight, height, monthly family income, basic health insurance, smoking status, alcohol consumption, frequency of physical activity, history of KOA, and history of knee surgery. Body mass index (BMI, in kg/m 2 ) was calculated for each patient. Using the BMI cut-off values reported for the Chinese population, patients were classi ed as follows: underweight (< 18.5), normal weight (18.5-23.9), overweight (24.0-27.9), and obese (≥ 28).

Knee Injury and Osteoarthritis Outcome Score
The Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) is a short version of the original KOOS. It is a self-administered instrument that measures the outcomes of impairment, disability, and handicap after knee injury and comprises seven dimensions, each of which is scored from 0 to 4 for the degree of di culty (0, none; 1, slight; 2, moderate; 3, very; and 4, extreme). The original total score ranges from 0 to 28, with a higher score indicating better joint function (25). The KOOS-PS standard score is obtained by converting the score formula speci ed by the scale and ranges from 0 to 100 (13).
Visual analogue pain scale score Patients' subjective perception of pain was estimated using the visual analogue scale (VAS) score, which is widely used and determined by measuring the distance on a 10-cm line between the "no pain" anchor and the mark made by the patient. Patients use a vertical line to mark their current level of knee pain.
Scores range from 0 to 10, and a higher score indicates greater pain intensity.

European Quality of Life Five Dimension Five Level scale
The European Quality of Life Five Dimension Five Level (EQ-5D-5L) scale is a standardised instrument developed by the EuroQol group to measure health status and is widely used internationally (26, 27). It comprises ve dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on a 5-point scale (none, not di cult; slight, a little di cult; moderate, some di culty; severe, very di cult; or extreme, impossible). The scores obtained were converted into a total score using the Chinese scoring system and ranged from − 0.391 to 1.000, with higher scores representing a better health status.

Reliability
Internal consistency was measured using the Cronbach's alpha coe cient. An alpha value between 0.70 and 0.95 was considered to indicate acceptable reliability. The Cronbach's coe cients for the ve measurements of the KOOS-PS scale and ve measurements of the EQ-5D-5L scale are listed in Table 1.

Statistical analyses
Continuous variables are summarised as the mean and standard deviation, and categorical variables are shown as the frequency (percentage). Categorical variables were compared using Pearson's test, and continuous variables were compared using the Student's t-test or Wilcoxon test. Statistical signi cance was set at a p-value of < 0.05. The Spearman's correlation coe cient was used to describe the correlation between the KOOS-PS and EQ-5D-5L scores at each time point. An unconditional growth mixture model (GMM) with free estimates of factor loadings was tted to the EQ-5D-5L, KOOS-PS, and knee pain scores. A conditional GMM was tted to the EQ-5D-5L score; the intercept and slope terms for the KOOS-PS were then used as covariables to t the conditional GMM for the EQ-5D-5L score. The categorical latent variables of the EQ-5D-5L were used as the grouping variables. Univariable and multivariable logistic regression models were used to explore the factors associated with the EQ-5D-5L score. The multivariable logistic regression model was established by including variables with a p-value < 0.1. Monthly family income, exercise, KOOS-PS_I (the intercept term of KOOS-PS), KOOS-PS_S (the slope term of KOOS-PS), and VAS_C were independent variables, and EQ-5D-5L_C was the dependent variable. VAS_C and EQ-5D-5L_C represent categorical latent variables. R 3.6.2 was used for data cleaning, statistical description, and regression analysis, and Mplus 8.3 software was used for the GMM analysis.

Patient characteristics
The patient characteristics are presented in Table 2  Changes in EQ-5D-5L and KOOS-PS across ve waves Table 3 shows the changes in HRQoL and knee function over time, as assessed by the EQ-5D-5L and KOOS-PS scores. In comparison with preoperative values, HRQoL and knee function scores were lower on postoperative day 7 but were signi cantly improved by 6 months after surgery. There was a signi cant correlation between the KOOS-PS sore and EQ-5D-5L score preoperatively, at 7 days, and at 1, 3, and 6 months postoperatively, with Spearman correlation coe cients of 0.568, 0.654, 0.579, 0.525, and 0.538 (p < 0.001), respectively. and 2, Additional les 1); therefore, an unconditional GMM was used to identify the growth trajectory of EQ-5D-5L scores and its heterogeneity. The same method was used to explore the growth trajectory and heterogeneity of the KOOS-PS and pain-VAS scores. The model tting results (Supplementary Tables 1-4, Additional les 1) showed that the best classi cations for EQ-5D-5L, KOOS-PS, and VAS pain scores were 3-class, 1-class (latent growth curve modelling), and 2-class, respectively. We further examined the tted linear-free-estimate GMM (2-class, 3-class, and 4-class) and found that the KOOS-PS_I and KOOS-PS_S simultaneously had a signi cant effect on the categorical latent variables as well as the continuous intercept term (EQ-5D-5L_I) and slope term (EQ-5D-5L_S) for the EQ-5D-5L (28-30). Therefore, the 2-class GMM was deemed to be the best tting model for representing the HRQoL trajectories over a period of ve waves. The individual growth trajectories of these two classes are shown in Supplementary Figs. 3 and 4 (Additional les1). The average trajectory of the 2-class GMM-C is shown in Fig. 2. Patients in whom the average HRQoL trajectory (EQ-5D-5L) improved markedly and rapidly after TKA were classi ed as the "rising" group, and those in whom the increase in the HRQoL trajectory was slower and less marked were classi ed as the "stable" group.
Parameter estimates of HRQoL in 2-class GMM Supplementary Table 5 (Additional le1) presents the parameter estimates for the selected 2-class GMM of the EQ-5D-5L scores. In the stable group (n = 45), the baseline EQ-5D-5L scores (EQ-5D-5L_I) was positively associated with the baseline KOOS-PS scores (KOOS-PSI) (beta = 0.021, p < 0.001), suggesting that HRQoL was positively associated with the KOOS-PSI preoperatively. However, the baseline KOOS-PS scores were not signi cantly associated with changes in the EQ-5D-5L scores (p = 0.518). The results of the heterogeneity analysis in the stable group also showed that there were differences in the baseline HRQoL scores among individuals (residual mean, -0.446, p = 0.044; and residual variance, -0.023, p = 0.014), although there were no signi cant differences in the change in HRQoL among individuals (p = 0.569 and p = 0.742). The intercept was not correlated with the slope (p = 0.972).

Latent HRQoL variables as risk factors
In univariable logistic regression analysis, the KOOS-PS knee function score, monthly family income, amount of daily exercise, and VAS_C were associated with being in the rising EQ-5D-5L group ( The odds of being in the rising group were higher in patients who exercised for approximately 30 min daily than in those who did not (OR 2.95, 95% CI 1.06-9.02). However, when daily exercise was performed for more than 30 min, the odds were not signi cant (OR 1.62, 95% CI 0.66-4.02), using patients who did not exercise as reference. For patients with a decreasing VAS pain score, the odds of being in the rising group were higher than in those with a stable VAS pain score (OR 6.09, 95% CI 2.72-14.07). Moreover, we found that the odds of being in the rising group increased with higher KOOS-PS scores (Table 5).

Discussion
This study aimed to identify any population heterogeneity in factors in uencing changes in the HRQoL of patients with KOA that might be used to develop individualised treatment strategies.
We found that patients showed improvement in knee function and HRQoL after TKA, which is consistent with the ndings of Zhang et al. (31) and Neuprez et al. (32). The trajectory for EQ-5D-5L indicated that patients experienced a cycle of change in knee function and HRQoL after TKA. HRQoL would be expected to deteriorate for a short period immediately after TKA due to postoperative bed rest, limited knee function, and wound pain. Osteotomy, unicompartmental knee arthroplasty, TKA, and arthroscopic surgery can all improve functional scores in patients with KOA; however, follow-up studies indicate that TKA is better than the other interventions in relieving knee pain and improving knee function in the long term (33). HRQoL is not only an indicator of physical tness but also a re ection of psychological and socioeconomic status. Therefore, mental well-being may be almost as important as physical discomfort and activity restriction in determining self-reported outcomes and HRQoL after TKA (34,35). High preoperative expectations are associated with clinical improvement, including pain reduction (36). Maintaining a stable emotional state and a positive attitude toward short-term discomfort are important in patients undergoing TKA. Additionally, patients should follow medical advice strictly and cooperate with examinations, treatment, and rehabilitation exercises. Doctors and rehabilitation therapists should strengthen preoperative communication and psychological counselling for these patients. Appropriate guidance and care are essential to gain the full trust of patients with KOA and boost their con dence, which is essential to the success of treatment (24).
In this study, the results of 2-class GMM indicate that the higher the baseline knee function score, the more rapid the improvement in knee function and HRQoL after surgery. This nding suggests that patients with better knee function at baseline would derive the most bene t from surgery, which is consistent with the ndings of Fortin et al. (37). Age-related neuromotor changes lead to skeletal muscle weakness and reduced power. Muscle strength and power have been reported to decrease by at least 24% in TKA recipients compared with those in controls (38). However, more demanding rehabilitation protocols may help to overcome these de cits. Postoperative rehabilitation following TKA would make a substantial contribution to patient outcomes, including a shorter hospital stay and fewer complications. Early rehabilitation, telerehabilitation, outpatient therapy, and high intensity and high velocity exercise may be bene cial to reduce pain intensity and joint stiffness (38). Therefore, joint rehabilitation training and functional exercises should be initiated under medical supervision as soon as possible in these patients. An improved focus on patient rehabilitation after discharge, including home-based exercise and dietary guidance, may also be needed to maximise the bene ts of surgery.
In this study, patients with a monthly family income of < 2000 yuan had less improvement in postoperative knee function and HRQoL than their more a uent counterparts, and this difference was observed over a long period of time. Most patients were over the age of 50 years and those with a monthly family income of < 2000 yuan were mostly agricultural or migrant workers. These individuals generally have less health knowledge, are of lower socioeconomic status, and have relatively poor selfmanagement skills (39). For nancial reasons, they are less likely to protect their knees when performing daily activities and are more likely to opt for less expensive drugs, medical consumables, and therapies. Furthermore, they often return to work prematurely without adequate rest and rehabilitation after surgery.
Patients in this study who exercised for approximately 30 min daily had a better outcome than those who did not exercise. An appropriate amount of regular exercise both protects and improves knee function in patients with KOA and accelerates postoperative recovery. However, care must be taken to avoid excessive exercise, which can damage the reconstructed knee.
Pain was also identi ed to affect the outcome of TKA, which is consistent with previous reports (40,41). Pain severely affects both mobility and mental well-being in patients with KOA. Therefore, adequate perioperative pain management is important in these patients. A study found that some patients with KOA and mild pain do not ask for pain relief soon enough and miss the opportunity for intervention in the early stage of in ammation (41), which led to worsening of the disease. Pain should be controlled effectively in the early stages of KOA, with consideration of interventions such as physical therapy to avoid progression of acute pain to uncontrollable chronic pain.

Consent for publication
Each patient included in this study received written information and no patient objected to this study.

Availability of data and materials
Data are available to request.

Competing interests
The authors declare that they have no competing interests.

Role of funding source
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors' contributions
All authors contributed to the conception and design of the study, or acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content and approved the nal manuscript for publication. JC (erin2009@smu.edu.cn) takes responsibility for the integrity of the work as a whole, from inception to nished article. Figure 1 Flow chart showing the study screening and enrolment process. KOA, knee osteoarthritis; TKA, total knee arthroplasty