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PLOS Medicine logoLink to PLOS Medicine
. 2021 Jul 16;18(7):e1003704. doi: 10.1371/journal.pmed.1003704

Obesity and revision surgery, mortality, and patient-reported outcomes after primary knee replacement surgery in the National Joint Registry: A UK cohort study

Jonathan Thomas Evans 1,‡,*, Sofia Mouchti 1,, Ashley William Blom 1,2, Jeremy Mark Wilkinson 3, Michael Richard Whitehouse 1,2, Andrew Beswick 1, Andrew Judge 1,2,4
Editor: Esa Jämsen5
PMCID: PMC8284626  PMID: 34270557

Abstract

Background

One in 10 people in the United Kingdom will need a total knee replacement (TKR) during their lifetime. Access to this life-changing operation has recently been restricted based on body mass index (BMI) due to belief that high BMI may lead to poorer outcomes. We investigated the associations between BMI and revision surgery, mortality, and pain/function using what we believe to be the world’s largest joint replacement registry.

Methods and findings

We analysed 493,710 TKRs in the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man from 2005 to 2016 to investigate 90-day mortality and 10-year cumulative revision. Hospital Episodes Statistics (HES) and Patient Reported Outcome Measures (PROMs) databases were linked to the NJR to investigate change in Oxford Knee Score (OKS) 6 months postoperatively.

After adjustment for age, sex, American Society of Anaesthesiologists (ASA) grade, indication for operation, year of primary TKR, and fixation type, patients with high BMI were more likely to undergo revision surgery within 10 years compared to those with “normal” BMI (obese class II hazard ratio (HR) 1.21, 95% CI: 1.10, 1.32 (p < 0.001) and obese class III HR 1.13, 95% CI: 1.02, 1.26 (p = 0.026)). All BMI classes had revision estimates within the recognised 10-year benchmark of 5%. Overweight and obese class I patients had lower mortality than patients with “normal” BMI (HR 0.76, 95% CI: 0.65, 0.90 (p = 0.001) and HR 0.69, 95% CI: 0.58, 0.82 (p < 0.001)). All BMI categories saw absolute increases in OKS after 6 months (range 18–20 points). The relative improvement in OKS was lower in overweight and obese patients than those with “normal” BMI, but the difference was below the minimal detectable change (MDC; 4 points). The main limitations were missing BMI particularly in the early years of data collection and a potential selection bias effect of surgeons selecting the fitter patients with raised BMI for surgery.

Conclusions

Given revision estimates in all BMI groups below the recognised threshold, no evidence of increased mortality, and difference in change in OKS below the MDC, this large national registry shows no evidence of poorer outcomes in patients with high BMI. This study does not support rationing of TKR based on increased BMI.


Jonathan Evans and co-workers study associations between patients’ weight and outcomes of total knee replacement in the UK.

Author summary

Why was this study done?

  • While total knee replacements (TKRs) are generally considered safe and effective, it has been suggested that patients with high body mass index (BMI) are at increased risk of poor outcomes, leading to policies restricting who is referred for surgery.

  • Previous studies of the impact of BMI have used smaller datasets or have focused on a single outcome rather than the wider focus of this article, which includes mortality, implant survival, and patient-reported outcomes.

  • We aimed to investigate whether patients with a raised BMI operated on within the National Joint Registry (NJR) had demonstrably worse outcomes following TKR.

What did the researchers do and find?

  • We analysed 493,710 TKRs implanted between 2005 and 2016 to investigate the proportion of patients that died within 90 days, how many implants needed revising (redo surgery) after 10 years, and the changes between preoperative and 6-month postoperative Oxford Knee Score (OKS).

  • Patients with raised BMI (according to the World Health Organization (WHO) categories) were compared to those with a “normal” BMI.

  • Patients in the “overweight” and “obese” groups had a lower 90-day mortality than those with “normal” BMI.

  • TKR in patients with raised BMI were more likely to have been revised after 10 years, although the cumulative revision estimate in all groups was below the benchmark of 5% generally considered to be acceptable.

  • All patient groups demonstrated an improvement in OKS after 6 months. The “overweight” and “obese” groups demonstrated a smaller relative improvement compared to the “normal” group; however, this relative difference was below the threshold considered to be clinically meaningful.

What do these findings mean?

  • There does not appear to be any evidence to support clinically relevant worse outcomes following TKR for patients with a raised BMI in the NJR between 2005 and 2016.

  • These findings do not support restriction of referral for knee replacement based on BMI alone. It appears that even if some patients with raised BMI are at risk of poorer outcomes, the outcomes remain acceptable by contemporary standards, and the selection process of orthopaedic surgeons is effective at identifying the correct patients to operate on at a population level.

Introduction

Total knee replacement (TKR) is one of the most common orthopaedic operations and is generally considered to be both safe, cost-effective, and clinically effective in reducing symptoms of pain and functional limitation in most patients [1,2]. Almost 1 in 10 people in the UK can expect to receive a TKR at some point in their lifetime, and approximately 100,000 have been performed in the UK each year for the last 4 years [35]. The main reasons for performing a TKR are joint pain and/or functional limitation in combination with radiographic evidence of arthritis; despite this, there is no consensus on the severity of symptoms that indicate the need for surgery [2,6,7]. Performing TKRs on the wrong patients may lead to poorer outcomes and lead to early revision surgery, which is both less effective than primary surgery and costly to patients and the health service [8,9]. Specific risk factors for poor outcomes that have previously been described include greater age, comorbidities, frailty, high body mass index (BMI), psychological factors, and the patient having a poor expectation of the success of surgery [1013]. With an ageing population, the number of people having a TKR can be expected to increase, placing an increasing burden on the National Health Service (NHS) in respect of funding and capacity [14].

There is growing evidence that some commissioners of health services in the UK are either restricting access to TKR for patients with high BMI or encouraging weight loss prior to referral for surgery [15,16]. This may be as a result of a belief that these patients are at a higher risk of complications. Surgeons may express concerns that increased load on a prosthesis increases the risk of failure due to loosening or wear or that the operation itself is more difficult, resulting in an increase in perioperative problems [17]. This is despite evidence that overall, the absolute risk of postoperative complications within the first 6 months of TKR is low in patients with a high BMI [18].

National guidance in the UK is clear that in patients with clinical osteoarthritis, while interventions to achieve weight loss are recommended, a high BMI and other patient specific factors should not be barriers to referral for joint replacement [6]. In contrast to this, there is some evidence from joint registries, observational cohort studies, and routine hospital admission data that high BMI is associated with poorer outcomes with regard to pain and function, mortality, complications, and need for revision surgery [18,19]. Whether these observed associations transfer to be clinically meaningful is as yet unclear.

Using data from the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man, our aim is to describe the association of BMI at the time of surgery with revision after 10 years, 90-day mortality, and patient-reported outcomes 6 months following primary TKR and to consider the clinical importance of any observed association. This is of importance for both future commissioning and clinical decision-making.

Methods

Study design and data source

We performed an observational cohort study using data obtained from the NJR. Since April 2009, Patient Reported Outcome Measures (PROMs) data have been collected on TKRs performed in public hospitals in England, most notably for this study, preoperative and 6-month postoperative Oxford Knee Scores (OKSs) [20].

Data linkages, participants, and inclusion criteria

The NJR started collecting BMI data on April 1, 2005, and we investigated patients undergoing primary TKR from this date up to and including December 31, 2016 for revision and mortality outcomes. Data were excluded on patients with missing or implausible BMI, age or sex, unspecified TKR fixation type, TKRs performed for trauma as well as for patients without a specified NHS number (preventing linkage) or with an unknown indication. Linkage between PROMs and the NJR was made via the Hospital Episodes Statistics (HES) database, which records details of all hospital admissions in England using the same exclusion criteria. HES data and subsequently PROMs data were only available up to December 30, 2014.

Outcomes

The outcome variables for this study are revision surgery (defined as the addition, removal, or modification of any part of the construct) [3], mortality within 90 days of the primary operation, and patient-reported outcome assessed using the change in OKS after 6 months. The OKS is a patient-completed questionnaire that assesses knee pain and function with 12 questions, each scored from 0 to 4, completed using Likert scales, and the scores are summed to give a score from 0 (worst) to 48 (best) [20]. In cohort studies (such as the NJR), the minimal detectable change (MDC) in OKS at the group level has been shown to be 4 points [21].

Exposure variable

The primary exposure of interest is BMI at the time of operation defined according to the World Health Organization (WHO) International Classification: <18.5 kg/m2 (underweight); 18.5 to 24.99 kg/m2 (normal weight); 25 to 29.99 kg/m2 (overweight); 30 to 34.99 kg/m2 (obese class I); 35 to 39.99 kg/m2 (obese class II); and >40 kg/m2 (obese class III).

Confounding variables

Confounding variables considered included age at primary TKR grouped as <50, 50 to 54, 55 to 59, 60 to 64, 65 to 69, 70 to 74, 75 to 79, 80 to 84, and ≥85 measured in years; sex; American Society of Anaesthesiologists (ASA) physical status classification grouped as P1, P2, P3, or P4 to P5; year of receiving the primary TKR grouped as 2005 to 2007 and as individual years between 2008 and 2016; cemented, uncemented, or hybrid fixation; reason for operation classified as osteoarthritis, osteoarthritis plus another indication, or other indications only; quintiles of the Index of Multiple Deprivation (IMD) coded between 1 (most deprived) and 5 (least deprived); Charlson comorbidity index grouped as 0 (no comorbidities), 1 (mild), 2 (moderate), and 3+ (severe) comorbidities; and preoperative EQ5D 3L Anxiety/Depression domain. The IMD is the official measure of relative deprivation for small areas (Lower Layer Super Output Areas) in England. The measure is calculated using 7 domains including income, employment, education, health, crime, and environment. It ranks every small area from 1 (most deprived) to 32,844 (least deprived) [22].

Statistical analysis

We plotted Kaplan–Meier estimates with risk tables to explore cumulative probability of revision up to 11 years and death up to 90 days for the BMI categories. Time zero was considered the time of the primary operation, patients were considered to have exited the study after the first revision episode was observed, and patients were censored upon death and administratively censored on December 31, 2016.

We used flexible parametric survival models as described by Royston and Parmar to investigate the association between BMI category and the risk of revision [23]. To choose a suitable scale and baseline complexity for the model, we fitted a univariable model (on the BMI category). We assessed choice of scale and number of knots for baseline spline function by inspecting the Akaike information criterion (AIC) and Bayes information criterion (BIC) statistics. We used Cox proportional hazards regression models to investigate 90-day mortality. We adjusted for age, sex, ASA grade, indication for operation, and year of primary TKR. The assumption of proportionality of hazards was assessed visually and through the use of Schoenfeld residuals.

Linear regression modelling (ANCOVA) is used to describe the association of BMI on 6-month OKS, adjusting for preoperative OKS as a covariate in the model and known available confounders. As there was evidence of heteroscedasticity (variance of the residuals is nonconstant), robust standard errors were used with the sandwich variance estimator [24]. Stata 14.2 was used for all analyses (Stata Statistical Software: Release 14, Stata, College Station, Texas, United States of America).

For survival outcomes, each knee replacement was treated as an individual; this is possible given the nature of reporting of both primary and revisions in the NJR. For PROMs and mortality analyses, however, same-day knee replacements could not be interpreted individually. For this reason, in same-day TKRs, only 1 was selected at random to contribute to the analyses to avoid duplication of data.

Sensitivity analysis

We further adjusted for confounders that can be derived only from the subset of patients with linked HES data (Charlson comorbidity score and IMD deprivation score) to estimate revision and mortality. In the PROMs analysis, this included further adjustment for the preoperative EQ5D 3L Anxiety/Depression question score. In response to peer review, all models for primary outcomes were run with BMI as a continuous variable using restricted cubic splines with knots at cutoffs of WHO categories.

Missing data

A comparison of demographic characteristics of participants with and without a recorded BMI was conducted to investigate the potential for selection bias.

Planning of analyses

The analysis plan was made prior to the start of all analyses and agreed among coauthors. No data-driven changes to the analysis plan were made. An additional sensitivity analysis with BMI as a continuous variable using splines (at WHO cutoffs) to investigate nonlinearity was included in response to peer review.

Reporting of the study was in keeping with guidance provided in the Reporting of studies Conducted using Observational Routinely-collected Data (RECORD) statement (S1 Checklist) [25].

Approval for this study was granted by the NJR research subcommittee reference. Written consent was granted by patients for inclusion of their data and its use in research within the NJR for England, Wales, Northern Ireland, and the Isle of Man.

Results

Participants

After exclusions, 493,710 TKRs remained to investigate revisions and 90-day mortality (Fig 1), with a maximum follow-up time of 11 years and a mean of 3.8 years. This dataset accounted for 56% of the total number of primary TKRs recorded in the NJR to December 31, 2016.

Fig 1. Flow diagram showing the availability of mortality and revision data after primary TKR.

Fig 1

BMI, body mass index; HES, Hospital Episodes Statistics; NHS, National Health Service; TKR, total knee replacement.

In linked PROMs, HES, and NJR datasets, 237,288 primary TKR operations were performed between March 26, 2009 and December 30, 2014 (S1 Fig). After applying the exclusion criteria, 165,193 primary TKR were available to investigate the association of BMI with the OKS patient-reported outcome.

Descriptive data

Overall, 57% of operations included in the NJR between 2005 and 2016 had BMI recorded. Completeness of overall BMI data in the NJR has improved over time; in 2005, of the 31,733 operations, 17.0% had BMI data, compared to 79.5% of the 88,078 operations in 2016. Demographics were similar between the 2 datasets with either complete or incomplete BMI data (Table 1).

Table 1. Distribution of sex, ASA grade, fixation type, and age in datasets with complete and incomplete BMI records.

Complete (N = 493,710) Incomplete (N = 384,481)
N % N %
Sex Female 283,161 57.4 221,450 57.6
Male 210,549 42.6 163,030 42.4
Missing 0 0 1 0
ASA grade P1 48,134 9.75 51,405 13.4
P2 362,745 73.5 272,432 70.9
P3 81,342 16.5 58,931 15.3
P4–P5 1,489 0.3 1,713 0.45
Fixation type Cemented 473,303 95.9 355,270 92.4
Uncemented 17,380 3.52 23,340 6.07
Hybrid 3,027 0.61 5,871 1.53
Age in years <50 9,883 2 8,268 2.15
50–54 20,024 4.06 14,131 3.68
55–59 40,688 8.24 31,392 8.16
60–64 72,014 14.6 54,850 14.3
65–69 96,459 19.5 71,053 18.5
70–74 98,844 20 77,452 20.1
75–79 85,619 17.3 70,086 18.2
80–84 50,293 10.2 40,999 10.7
≥85 19,886 4.03 16,250 4.23

ASA, American Society of Anaesthesiologists; BMI, body mass index.

Patient characteristics in different BMI categories are summarised in Table 2. Overall, 55.4% of patients were obese (BMI ≥30 kg/m2), and 0.3% were underweight (BMI <18.5 kg/m2). Low ASA grades were more frequently observed in people with BMI <35 kg/m2 (WHO obese class I or below), while higher ASA grades were more common in underweight or obese class II and III patients (BMI <18.5 and ≥35 kg/m2). The majority (>95%) of TKRs were cemented in all BMI categories.

Table 2. Patient characteristics for sex, age, ASA grade, and fixation type by BMI category.

<18.5 kg/m2 18.5–24.99 kg/m2 25–29.99 kg/m2 30–34.99 kg/m2 35–39.99 kg/m2 ≥40 kg/m2
n (%) 1,338 (0.27) 49,860 (10.10) 168,947 (34.22) 159,056 (32.22) 80,166 (16.24) 34,343 (6.96)
Sex n (%) Female 1,025 (76.61) 30,666 (61.50) 85,150 (50.40) 87,863 (55.24) 52,759 (65.81) 25,698 (74.83)
Male 313 (23.39) 19,194 (38.50) 83,797 (49.60) 71,193 (44.76) 27,407 (34.19) 8,645 (25.17)
Age median (IQR) Female 74 (66, 80) 74 (67, 80) 73 (66, 78) 70 (64, 76) 67 (61, 73) 64 (58, 70)
Male 70 (63, 78) 74 (67, 80) 71 (65, 77) 69 (63, 74) 66 (61, 72) 64 (59, 69)
ASA grade n (%) P1 109 (8.15) 6,734 (13.51) 21,105 (12.49) 14,719 (9.25) 4,443 (5.54) 1,024 (2.98)
P2 904 (67.56) 35,812 (71.83) 125,847 (74.49) 120,151 (75.54) 59,200 (73.85) 20,831 (60.66)
P3 317 (23.69) 7,145 (14.33) 21,618 (12.80) 23,806 (14.97) 16,265 (20.29) 12,191 (35.50)
P4–P5 8 (0.60) 169 (0.34) 377 (0.22) 380 (0.24) 258 (0.32) 297 (0.86)
Fixation type n (%) Cemented 1,306 (97.61) 47,889 (96.05) 161,854 (95.80) 152,224 (95.70) 76,958 (96.00) 33,072 (96.30)
Uncemented 22 (1.64) 1,640 (3.29) 6,115 (3.62) 5,806 (3.65) 2,752 (3.43) 1,045 (3.04)
Hybrid 10 (0.75) 331 (0.66) 978 (0.58) 1,026 (0.65) 456 (0.57) 226 (0.66)

ASA, American Society of Anaesthesiologists; BMI, body mass index.

Revision

Fig 2 demonstrates that the cumulative probability of revision rises with increasing BMI at the time of operation. Table 3 shows the number of knee replacements “at risk” (not yet failed or censored for death or administratively) at each time point for each BMI class in the original dataset, from which the model was built. After 10 years, patients with BMI ≥40 kg/m2 had 4.0% (95% CI: 3.6, 4.5) cumulative probability of revision compared with 2.8% (95% CI: 2.5, 3.3) in those with BMI 18.5 to 24.99 kg/m2 (Table 4). Table 5 presents the hazard ratios (HRs) for each BMI group (derived from the flexible parametric models) for revision relative to patients with BMI of 18.5 to 24.99 kg/m2 encompassing the full 11 years of follow-up. The adjusted model shows that patients with BMI 30 to 34.99 kg/m2, 35 to 39.99 kg/m2, and ≥40 kg/m2 were 8% (HR 1.08, 95% CI: 0.99, 1.18 (p = 0.073)), 21% (HR 1.21, 95% CI: 1.10, 1.32 (p < 0.001)), and 13% (HR 1.13, 95% CI: 1.02, 1.26 (p = 0.026)) more likely to undergo a revision than patients with BMI 18.5 to 24.99 kg/m2, respectively, although it should be noted that the confidence intervals for the 30 to 34.99 kg/m2 category do cross the null value. Fig 3 shows the hazard of revision when BMI is modelled as a continuous variable with splines at WHO cutoffs. This model is consistent with models using BMI as a categorical variable.

Fig 2. Flexible parametric model estimates of cumulative probability of revision up to 11 years after primary TKR by BMI category.

Fig 2

BMI, body mass index; TKR, total knee replacement.

Table 3. Numbers of knee replacements at risk at specified time points in the dataset from which the model was built.

Years since primary operation
0 3 5 7 8 9 10 11
Underweight 1,338 807 505 236 153 66 20 0
Normal 49,860 28,400 17,064 8,395 8,395 2,085 199 36
Overweight 168,947 95,567 57,276 27,243 27,243 6,029 2,275 115
Obese class I 159,056 88,937 52,401 24,622 24,622 5,019 1,878 106
Obese class II 80,166 43,631 25,254 11,343 11,343 2,157 758 52
Obese class III 343,433 18,672 10,728 4,752 4,752 917 336 21

Table 4. Median and IQR of the pre- and postoperative OKS, cumulative percentage probability (KM estimates) of revision with 95% CI at 3, 5, 7, and 10 years, and cumulative percentage probability of mortality after 90 days (KM estimates) with 95% CI at 30, 60, and 90 days by BMI category.

<18.5 kg/m2 18.5–24.99 kg/m2 25–29.99 kg/m2 30–34.99 kg/m2 35–39.99 kg/m2 ≥40 kg/m2
OKS median (IQR)
Preoperative 16 (10, 23)
(n = 386)
20 (14, 26)
(n = 15,319)
20 (14, 25)
(n = 55,001)
18 (13, 24)
(n = 53,496)
16 (11, 21)
(n = 27,498)
14 (9, 19)
(n = 11,608)
Postoperative 36 (28, 42)
(n = 293)
39 (31, 44)
(n = 12,807)
38 (31, 44)
(n = 46,927)
37 (29, 42)
(n = 44,549)
35 (26, 41)
(n = 22,176)
33 (24, 40)
(n = 8,977)
Cumulative probability of revision (95% CI)
Years since primary TKR 3 1.14 (0.65, 2.01) 1.24 (1.14, 1.36) 1.38 (1.32, 1.45) 1.59 (1.52, 1.66) 1.95 (1.84, 2.06) 2.06 (1.89, 2.24)
5 1.77 (1.07, 2.93) 1.70 (1.57, 1.85) 1.95 (1.87, 2.04) 2.21 (2.12, 2.30) 2.74 (2.60, 2.88) 2.87 (2.65, 3.10)
7 2.29 (1.39, 3.77) 2.10 (1.92, 2.28) 2.40 (2.30, 2.51) 2.68 (2.57, 2.79) 3.26 (3.09, 3.44) 3.49 (3.21, 3.79)
10 2.29 (1.39, 3.77) 2.83 (2.46, 3.26) 2.91 (2.74, 3.09) 3.27 (3.08, 3.47) 3.79 (3.50, 4.10) 4.02 (3.62, 4.47)
Cumulative probability of mortality (95% CI)
Days since primary TKR 30 0.38 (0.16, 0.90) 0.24 (0.21, 0.29) 0.16 (0.14, 0.18) 0.11 (0.10, 0.13) 0.11 (0.09, 0.14) 0.15 (0.11, 0.19)
60 0.68 (0.36, 1.31) 0.34 (0.30, 0.40) 0.23 (0.21, 0.25) 0.16 (0.14, 0.18) 0.17 (0.14, 0.20) 0.20 (0.16, 0.25)
90 0.76 (0.41, 1.41) 0.46 (0.41, 0.53) 0.29 (0.27, 0.32) 0.21 (0.19, 0.23) 0.21 (0.18, 0.25) 0.24 (0.19, 0.29)

BMI, body mass index; KM, Kaplan–Meier; OKS, Oxford Knee Score; TKR, total knee replacement.

Table 5. HR, 95% CI, and p-value for coefficients of BMI categories extracted from the flexible parametric models to investigate the association of BMI with revision after primary TKR.

Unadjusted model Adjusted model
HR 95% CI p-value HR 95% CI p-value
<18.5 kg/m2 0.96 (0.60, 1.54) 0.872 0.88 (0.55, 1.41) 0.608
18.5–24.99 kg/m2 (reference) 1.00 1.00
25–29.99 kg/m2 1.12 (1.03, 1.22) 0.007 1.05 (0.97, 1.14) 0.252
30–34.99 kg/m2 1.26 (1.16, 1.37) <0.001 1.08 (0.99, 1.18) 0.073
35–39.99 kg/m2 1.54 (1.41, 1.68) <0.001 1.21 (1.10, 1.32) <0.001
≥40 kg/m2 1.64 (1.48, 1.82) <0.001 1.13 (1.02, 1.26) 0.026

Adjusted model adjusts for age, sex, ASA grade, indication for operation, year of primary TKR, and fixation type. Both models were fitted on the hazard scale with 4 degrees of freedom.

ASA, American Society of Anaesthesiologists; BMI, body mass index; HR, hazard ratio; TKR, total knee replacement.

Fig 3. Hazard of revision within 11 years of TKR relative to patients with BMI of 22.5 modelled using flexible parametric survival analysis using BMI as a continuous variable with restricted cubic splines at cutoffs of WHO criteria.

Fig 3

BMI, body mass index; TKR, total knee replacement; WHO, World Health Organization.

Mortality

Table 6 shows that patients with BMI 25 to 29.99 kg/m2 and 30 to 34.99 kg/m2 had 24% (HR 0.76, 95% CI: 0.65, 0.90 (p = 0.001)) and 31% (HR 0.69, 95% CI: 0.58, 0.82 (p < 0.001)) lower 90-day mortality rate than patients with a normal BMI. Fig 4 demonstrates the mortality sensitivity analysis of the Cox model with BMI modelled as a continuous variable and is consistent with the findings form the model with BMI as a categorical variable.

Table 6. HR, 95% CI, and p-value for coefficients of BMI categories extracted by Cox proportional hazards models to investigate the association of BMI with mortality within 90 days of primary TKR.

Unadjusted model Adjusted model
HR 95% CI p-value HR 95% CI p-value
<18.5 kg/m2 1.65 (0.87, 3.10) 0.122 1.64 (0.87, 3.09) 0.128
18.5–24.99 kg/m2 (reference) 1.00 1.00
25–29.99 kg/m2 0.64 (0.55, 0.75) <0.001 0.76 (0.65, 0.90) 0.001
30–34.99 kg/m2 0.46 (0.39, 0.55) <0.001 0.69 (0.58, 0.82) <0.001
35–39.99 kg/m2 0.46 (0.38, 0.56) <0.001 0.88 (0.72, 1.09) 0.247
≥40 kg/m2 0.51 (0.40, 0.66) <0.001 1.17 (0.90, 1.54) 0.247

Adjusted model adjusts for age, sex, ASA grade, indication for operation, and year of primary TKR.

ASA, American Society of Anaesthesiologists; BMI, body mass index; HR, hazard ratio; TKR, total knee replacement.

Fig 4. Hazard of death within 90 days of TKR relative to patients with BMI of 22.5 modelled using Cox proportional hazards using BMI as a continuous variable with restricted cubic splines at cutoffs of WHO criteria.

Fig 4

BMI, body mass index; TKR, total knee replacement; WHO, World Health Organization.

Oxford Knee Score

The crude increase in OKS between pre- and 6-month postoperative assessments was similar across all BMI groups (range 18 to 20 points) and well above the minimal important change of 4/48 reported by Beard and colleagues (Table 4) [21]. After adjusting for age, sex, ASA, indication, fixation, year of operation, and anxiety status, the relative increase in OKS (between preoperative and 6-month postoperative) for patients with raised BMI was smaller relative to patients with a “normal” BMI (Table 7). Fig 5 shows the same model with BMI as a continuous variable using splines at WHO cutoffs.

Table 7. Estimates of BMI category coefficients to predict the mean increase or decrease in postoperative OKS.

Unadjusted model Adjusted model
Coefficient 95% CI p-value Coefficient 95% CI p-value
<18.5 kg/m2 −1.04 (−2.08, −0.01) 0.044 −0.74 (−1.75, 0.27) 0.150
18.5–24.99 kg/m2 (reference) 0.00 0.00
25–29.99 kg/m2 −0.24 (−0.42, −0.07) 0.005 −0.35 (−0.52, −0.18) 0.001
30–34.99 kg/m2 −1.07 (−1.24, −0.89) <0.001 −1.10 (−1.27, −0.92) <0.001
35–39.99 kg/m2 −1.96 (−2.16, −1.76) <0.001 −1.82 (−2.02, −1.61) <0.001
≥40 kg/m2 −2.83 (−3.07, −2.58) <0.001 −2.20 (−2.46, −1.93) <0.001

Adjusted model adjusts for age, sex, ASA grade, indication for operation, fixation type, year of primary TKR, and anxiety status.

ASA, American Society of Anaesthesiologists; BMI, body mass index; OKS, Oxford Knee Score; TKR, total knee replacement.

Fig 5. Change in mean OKS 6 months after TKR relative to patients with a BMI of 22.5 modelled using linear regression using BMI as a continuous variable with restricted cubic splines at cutoffs of WHO criteria.

Fig 5

Model adjusting for age, sex, ASA grade, indication for operation, fixation type, year of primary TKR, and anxiety status. ASA, American Society of Anaesthesiologists; BMI, body mass index; OKS, Oxford Knee Score; TKR, total knee replacement; WHO, World Health Organization.

Fig 6 illustrates the change between the pre- and postoperative OKS across the BMI categories. It highlights the substantial absolute change in OKS across all BMI categories compared to the small relative differences in the postoperative OKS between BMI categories.

Fig 6. Estimates of the postoperative score in relation to the preoperative OKS by BMI category.

Fig 6

We extracted these estimates from the fully adjusted model described in Table 7. BMI, body mass index; OKS, Oxford Knee Score.

Sensitivity analysis

Further analyses adjusting for additional confounders of deprivation and Charlson comorbidity did not change the findings with effect sizes being similar (S3 Table).

Discussion

Statement of principal findings

In this study using a large national joint replacement registry, after adjusting for age, sex, ASA, indication for operation, year of operation, and fixation type, patients classified as overweight or obese (BMI ≥25kg/m2) had a reduced 90-day mortality risk but an increased risk of revision surgery compared to those in the “normal” category. The 10-year cumulative risk of revision in patients with BMI 18.5 to 24 kg/m2 (reference group) was 2.8% and ranged from 2.3% in people with lowest BMI to 4.0% in those with the highest BMI. Patients in the “underweight” group (BMI <18.5kg/m2) had the highest mortality 90 days after TKR, but even in this large national arthroplasty registry dataset, the number of patients affected was small with 10 deaths in 1,338 patients. Regarding PROMs, all categories of BMI showed an absolute improvement in median OKS after 6 months compared to median preoperative scores. The relative improvement in OKS was slightly lower in overweight and obese patients at the time of surgery compared to patients with “normal” BMI, and the differences between groups were below the minimally important difference in change score. The 6-month absolute OKS appeared lower in higher BMI categories relatively, which reflects a lower starting point in these categories.

Strengths and weaknesses of the study

To our knowledge, this is the first study on obesity and knee replacement to examine all 3 domains of implant revision, mortality, and patient-reported outcomes. The failings of examining single domains have previously been highlighted, in that just because a TKR has not been revised does not necessarily mean it was a success [26]. We used what we believe is the largest joint replacement registry in the world, with near complete coverage of all operations performed in the target population. Analyses were not restricted to certain groups of patients or implant providers, allowing us to generalise the results to most patients undergoing elective primary TKR in England and Wales. The most notable limitation is the missing data on BMI. Before 2005, this variable was not collected, and between 2005 and 2016, the completeness of BMI data in our study dataset rose from 20.5% to 83.0%. Patient demographics were similar between operations with complete and non-complete BMIs, suggesting that there was unlikely to be responder bias. The main differences between groups (Table 1) were the distribution of patients between the ASA 1 and 2 groups and fixation type. Results of patients with ASA 1 and 2 tend to be similar, and so we do not feel this is likely to have biased results. More patients with missing BMI had cementless or hybrid fixation compared to those with BMI reported. Given the NJR annual report suggests poorer implant survival in cementless TKR [3], this difference could result in reduced survival overall and depending on how BMI is distributed among high-BMI patients could bias our results either way, although these fixation methods are only used in a small proportion of patients (4.1% of those with complete data and 7.6% of those with incomplete data). Overweight and obese patients receiving the operation are probably healthier and fitter than similar people not having surgery, which is likely to result in selection bias. As with all registry data, analyses are only as good as data entered; the first NJR data quality audit suggested that 95.7% of primary TKRs and 90.3% of revision TKRs were captured in financial year 204/15. Despite this high level of completeness, at the time of data collection, the NJR did not routinely capture operations where implants were not added, removed, or modified. This means that if a patient returned to theatre for an operation that did not involve the change of any implants, it would not have been captured by the NJR and would therefore not be reported by our study. It is possible that patients may require revision surgery but are deemed unsuitable because of comorbidities, and, as such, are not identified by the NJR as a failure. While this is a recognised limitation of registry research, it may be particularly relevant in this study if patients with high BMI at the time of primary surgery are considered at higher risk of developing future comorbidities that would render them less fit for revision surgery. OKS data were only available up to 6 months after TKR so we were unable to assess patient-reported pain and function as long postoperatively as we could describe revision outcomes. It is possible that recovery trajectories could vary according to BMI (i.e., higher BMI patients taking longer to recover). This could mean that patients in one particular group may not have achieved their peak postoperative outcome score by the 6-month point reported in this study. While the OKS has been widely validated, it has not been specifically validated in a solely high BMI group. This could potentially create some bias in comparison of subgroups of BMI if those with high BMI are more likely to score certain questions either higher or lower than patients with normal BMI. This study is observational in nature, and, as such, statements about causality cannot be made. Data used are routine data, and, as such, not collected specifically for inclusion in this study; this may lead to misclassification of covariates, missing data, and residual confounding.

Strengths and weaknesses of the study in relation to other studies

The results described here conflict with previously observed associations of higher BMI with increased all-cause mortality in general nonsurgical populations [27]. This may reflect a healthy surgery effect (obesity paradox), where those with high BMI selected for surgery are fitter with fewer comorbidities than those who do not present themselves, or are deemed unsuitable, for surgery. Our observation that mortality rates following primary TKR were similar or lower at high BMI is consistent with some previous studies [28]. A U-shaped relationship between BMI and mortality has been noted in 2 studies with higher mortality in underweight patients (BMI <18.5 kg/m2) compared to patients with a “normal” BMI according to WHO criteria [19,29]. Individual units or surgeons may employ different methods of determining a patient’s fitness for surgery as well as differing pre- and postoperative care for these patients. The data available in our study did not allow this to be explored in more depth. Our results do suggest that the processes already in place are suitable in identifying those high-BMI patients at increased risk of death and that restricting access to surgery at the point of referral is unlikely to be of benefit. In an analysis of data from over 54,000 patients undergoing primary TKR in the UK, there was a 1.02% increased hazard of revision for each unit of BMI, which is consistent with our study [30]. In a systematic review and meta-analysis including studies of primary TKR reported before February 2017, Pozzobon and colleagues note that in 5 studies, long-term pain, and, in 10 studies, disability, were greater in patients with BMI ≥30 kg/m2 compared with BMI <30 kg/m2 [31]. Due to the use of different outcome measures, the authors did not report whether these outcomes were clinically relevant. Our findings are generally conflicting with those of Chaudhry and colleagues, who in 2019 published a meta-analysis suggesting higher risk of revision and worse patient-reported outcomes in “severely, morbidly and super-obese patients” [32]. The main limitation of their analyses was the quality of included studies. Their conclusions focused on revision rate being driven by septic revisions, a subgroup we did not specifically look at in our study. Similarly, to Chaudhry and colleagues, we reported an increased revision risk in patients with higher BMI but concluded the cumulative revision estimate was still below the nationally recognised benchmark.

Meaning of the study: Possible explanations and implications for clinicians and policy makers

The results of this study are important for patients, surgeons, and healthcare commissioners, in that patients with a high BMI do not appear to have clinically relevant poorer outcomes compared to those with “normal” BMI. This is particularly relevant given the large absolute numbers of obese patients (273,565; 55.4%) that have received surgery and the incidence of symptomatic knee osteoarthritis and its progression increases with BMI [33]. Regardless of the observed differences in the 10-year cumulative revision estimates between groups, these estimates are all still comfortably within the nationally recognised benchmark of 5% at 10 years. Patients with higher than “normal” BMI showed smaller relative improvements in pain and function scores at 6 months after TKR, but this is outweighed by substantial improvements across all BMI categories. Improvements in OKS across categories ranged from 18 to 20 points, consistent with patient reporting of knee problems being “much better” than before surgery, and the difference between groups was lower than the clinically relevant difference of 4/48 reported by Beard and colleagues [21]. It is important to emphasise that, although we have detected statistically significant differences due to the very large sample size, they are not clinically meaningful differences.

Unanswered questions and future research

The main unanswered question from this work is what the OKS of patients will be at longer follow-up intervals, but these data are not yet available. The “healthy patient effect” that we propose in the setting of TKR for patients with higher than “normal” BMI also warrants further investigation. Patients with high BMI in combination with other risk factors (such as comorbidity) may have filtered out naturally in our cohort, suggesting that additional BMI-based filters are not needed at the referral stage. We did not investigate factors such as length of stay, which may have an impact on cost-effectiveness or primary TKR in this study. If BMI changes length of stay, it may lead to increased costs; therefore, future studies could investigate the effect of cost-effectiveness as an outcome. If it is accepted that BMI is not an appropriate rationing tool for TKR, then work looking at whether other instruments such as preoperative OKS assessments could be used may be useful.

Conclusions

In this study, revision, mortality, and pain and functional outcomes in obese patients appear to be similar to patients with a “normal” BMI at the time of surgery. Limiting access to TKR based on BMI thus appears to be unfounded.

Supporting information

S1 Checklist. STROBE and RECORD checklist.

RECORD, Reporting of studies Conducted using Observational Routinely-collected Data; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology.

(DOCX)

S1 Fig. Flowchart diagram describing the steps to create dataset for PROMs analyses.

PROMs, Patient Reported Outcome Measures.

(TIF)

S2 Fig. Cumulative probability of revision (KM estimates) with at risk table by BMI category.

BMI, body mass index; KM, Kaplan–Meier.

(TIF)

S3 Fig. Cumulative probability of 90-day mortality (KM estimates) with risk table by BMI category.

BMI, body mass index; KM, Kaplan–Meier.

(TIF)

S1 Table. Estimates from the flexible parametric survival model to investigate the association of BMI and revision using the NJR–HES dataset.

All the models were fitted on the hazard scale using 4 degrees of freedom. Adjusted models adjust for age, gender, type of fixation, ASA grade, year of having the primary operation, indication for operation, IMD, and Charlson comorbidity index. ASA, American Society of Anaesthesiologists; BMI, body mass index; HES, Hospital Episodes Statistics; IMD, Index of Multiple Deprivation; NJR, National Joint Registry; TKR, total knee replacement.

(DOCX)

S2 Table. Estimates from the Cox regression model to investigate the association of BMI and mortality within 90 days using the NJR–HES dataset.

Adjusted models adjusted for age, gender, ASA grade, year of primary TKR, indication for operation, IMD, and Charlson comorbidity index. ASA, American Society of Anaesthesiologists; BMI, body mass index; HES, Hospital Episodes Statistics; IMD, Index of Multiple Deprivation; NJR, National Joint Registry; TKR, total knee replacement.

(DOCX)

S3 Table. Coefficients of BMI categories to predict the mean increase or decrease on the postoperative OKS after 6 months.

Adjusted model adjusts for age, gender, ASA grade, indication for operation, fixation type, and year of receiving the primary TKR, anxiety status, Charlson score, and multiple deprivation index. ASA, American Society of Anaesthesiologists; BMI, body mass index; OKS, Oxford Knee Score; TKR, total knee replacement.

(DOCX)

Acknowledgments

We thank the patients and staff of all the hospitals who have contributed data to the National Joint Registry (NJR). We are grateful to the Healthcare Quality Improvement Partnership (HQIP), the National Joint Registry Steering Committee (NJRSC), and staff at the NJR Centre for facilitating this work.

Disclaimers: The views expressed represent those of the authors and do not necessarily reflect those of the NHS, the National Institute for Health Research, the Department of Health, NJRSC, or HQIP who do not vouch for how the information is presented.

Abbreviations

AIC

Akaike information criterion

ASA

American Society of Anaesthesiologists

BIC

Bayes information criterion

BMI

body mass index

HES

Hospital Episodes Statistics

HR

hazard ratio

IMD

Index of Multiple Deprivation

MDC

minimal detectable change

NHS

National Health Service

NJR

National Joint Registry

OKS

Oxford Knee Score

PROMs

Patient Reported Outcome Measures

RECORD

Reporting of studies Conducted using Observational Routinely-collected Data

TKR

total knee replacement

WHO

World Health Organization

Data Availability

Data are available from the NJR research subcommittee researchers who meet the criteria for access to confidential data. Access to the data used in this study can be requested via njrresearch@hqip.org.uk. Full details of how to request NJR data for research can be found at: http://www.njrcentre.org.uk/njrcentre/Research/Research-requests.

Funding Statement

JTE, SM, AWB, MRW, AB and AJ were supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Helen Howard

23 Sep 2020

Dear Dr Evans,

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Decision Letter 1

Emma Veitch

13 Nov 2020

Dear Dr. Evans,

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Comments from the reviewers:

Reviewer #1:

I confine my remarks to statistical aspects of this paper.

The general approach is fine and I like the use of new methods and the fact that the authors included all the covariates rather than doing some sort of model building.

However, I have a few issues to resolve before I can recommend publication.

The main issue is that BMI should not be categorized for the analysis (although the categories may be useful for some parts of presentation). Leave BMI as a number and investigate nonlinearity with a spline. The use of a spline on a categorized version of a variable is very limited. It limits estimation of knots - they have to happen at the cutoffs between categories. See *Regression Modeling Strategies* by Frank Harrell for more problems with categorizing continuous variables.

Grouping age has some of the same issue, but the authors use so many groups that it's probably OK. Still, why not leave age as "years"?

Why was year grouped the way it was? That would seem to force year to be categorical and would waste degrees of freedom (not really a big problem here) and make interpretation of any year effect harder.

Fig 2 The y axis should be rescaled to soimething like 0 to 5 or 6. As is, most of the graph is blank. This makes it harder to see the rela

Fig. 3. I don't like that the scales of the two axes are so different. The plot makes it look like there was equal improvement for all initial conditions, when, really, there was no improvement at the highest initial leves. I suggest either making both axes go from 0 to 50 or else a graph with initial score on the x axis and improvement on the y axis. This seems very important. The authors note that BMI isn't a useful predictor of success (and, as an overweight man who will probably need knee surgery, I appreciate that!) but another useful finiding here (which might make another paper) is that people with good initial OKS didn't really improve much.

Peter Flom

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Reviewer #2:

The authors have written a clear and logically constructed article suggesting the higher body mass index is associated with slightly higher revision rate but similar clinical improvement (in terms of Oxford Knee Score) after six months after primary knee replacement. The case numbers are clearly sufficient and the follow-up long enough to report revision rates. Nationally representative materials and appropriate statistical methodology can be also considered as strengths of this study. Unfortunately, there are also several issues to criticize. However, I believe the authors have good possibilities to satisfactorily respond to these concerns.

Major concerns:

1) I have troubles following the description of collection of the data and creating the datasets. I understand that revision data and clinical data come from different sources and are from different time periods, but presenting four (!) different flowcharts is confusing. Figure 1 of the manuscript is quite ok although I do not understand why to report the total number of TKRs since 2003 although included cases were from 2005-2016. I am also able to follow Figure 1 in the supplementary materials but do not understand the next flowchart Figure 2 at all (it ends up with figure 288,423 that is not mentioned anywhere else) and the last flowchart feels like repetition. Also, the different time periods are confusing and poorly explained acronyms (LM, HES) complicate interpretation. The authors should bear in mind that most readers are likely not familiar with the registers of the authors' country.

It is noteworthy that there are lots of missing data. About one third of cases were excluded because of missing BMI and there were exclusions for other reasons as well. I do not quite agree with the authors that excluded patients were comparable to the included ones. According to table 1, there were more patients with lower ASA and more cementless TKRs in the incomplete (i.e. excluded) group. Differences e.g. in comorbidity, type of operating unit and social status are not reported. It is also likely that patients responding to Oxford Knee Score represent a selected sample of patients (younger, uncomplicated and so on), limiting generalizability of the findings). These issues related to possible selection bias should be reported and discussed more thoroughly. Especially the results about lower mortality with higher BMIs indicate that in the obese groups there have been significant patient selection (and/or differences in pre- and perioperative care) that are not fully captured by the variables used in this study.

2) Validity and coverage of the data sources should be described. Although national registers usually cover primary joint replacements quite well, the coverage of revision joint replacements is usually poorer. From the viewpoint of the current study, prosthetic-joint infections represent a specific problem as their risk is higher in patients with highest BMI, and they can be managed with other means than full revision surgery especially in high-risk patients and in acute infections. One might have expected higher early revision rate in the most obese group because of PJIs. It is unclear how data about different confounding variables were collected, what is their completeness and coverage. Most readers may not be familiar with Multiple Deprivation Index and EQ5D, the coverage of latter of which could be expected to be limited.

3) The materials were collected until December 31, 2016, and the same date was the end of follow-up. Consequently, some of the patients had practically zero follow-up and they could not have experienced the outcomes that were of interest. Although for example in the analysis of deaths, Cox analysis (taking into account different follow-up times) was used appropriately, including also patients without sufficient follow-up in the denominator leads to falsely low absolute rates of e.g. deaths or revisions. Now that it is already year 2020, it is difficult to see, why the authors have not used more later data - or in the other hand, made the choice of materials so that all patients would have reasonable minimum follow-up (at least six months to get PROM data or more preferably one year).

There are also discrepancies in the observation period: methods section say that cases were included from 2005-2016, but flowcharts in the supplementary materials and results section also talk about period 2009-2014.

The adjustments used in the regression models are also described incompletely and/or contradictory: methods section lists several confounding factors but not all of them were used in all analyses, according to legends of 4-6 and the tables presented in supplemental materials. Most materials of supplementary materials are not referred to in the text. As there have been several multivariable models, statements like "fully adjusted model" are not accurate enough.

4) I'd appreciate more critical analysis and interpretation of the results and more thorough review of the literature.

- With all due respect, now the manuscript has a feeling that its aim is to support the view that BMI should not have a role in rationing knee replacement although earlier literature and also the current results might be interpreted to support the opposite view. There are a couple of recent meta-analyses (indicating poorer results with higher BMI) that have been ignored (Chaudhry et al. JBJS Rev 2019, Sun & Li Knee 2017, Si et al. Knee Surg Sports Traumatol Arthrosc 2015) - and considering numerous earlier reports, it should be articulated more clearly what are the news that the present study give (mid-term revision rates could be such). The present study is somewhat contradictory with earlier meta-analyses and reasons for these discrepancies should be commented.

- Early complications (not leading to revision joint replacement), possibly prolonged hospitalizations and particularly prosthetic-joint infections have not been taken into account in the present analysis, which should be discussed as a limitation as they affect the costs and hence cost-effectiveness and rationing of surgery. Also one further reason supporting conservative treatment rather than surgery is that weight loss and rehabilitation have been reported to ease the symptoms of osteoarthritis, making knee replacement possibly unnecessary at least for a while.

- The authors suggest that reporting revision rates, mortality and clinical outcome all in the same study is a strength of this study. Combining the three but analyzing them separately however does not necessary give any extra over separate and possibly more detailed studies. In the Discussion, the authors write "The failings of examining single domains have previously been highlighted, in that just because a TKR has not been revised does not necessarily mean it was a success." to reason combining the three outcomes. Because the present study analyzes clinical outcome after six months but revision rates up to 10 years, it does not overcome this problem, and problem with falsely low revision rate as a result of not performing revision in hight risk patients still remains a problem and should be acknowledged.

Minor concerns:

- References 8 and 9 are about hip replacements although there are suitable ones about knees as well.

- Age is a continuous variables. Why is it used as classified one?

- How (staged or same-day) bilateral knee replacements were dealt with? This is relevant both concerning the outcome analysis but also data linkage.

- Fulfillment of proportional hazards assumption should be commented in association with use of Cox regression analysis.

- Please, keep the order of analyzed outcomes the same throughout the manuscript (now OKS is mentioned first in the results section).

- What does BMI <0 mean?

- Y-axis in Figure 3 should start from zero or it should be indicated that it is cut.

- It seems that Figure 3 represents data from a linear model. In its current form its value is questinable and interpretation is difficult: I think it is not that certain that association is linear but instead from lower scores the improvent might be greater. Ceiling effect may also be present. Secondly, there is possibly variation in individual patients' responses and one might hypothesize that variation might be greater in the obese groups. I'd suggest replacing Figure 3 with information based on actual observations (change from pre to postop in different BMI categories and its variation).

- I's suggest using Kaplan-Meier analysis (instead of modelled curves of Figure 2) in the manuscript as results from adjusted models are already shown in the tables.

- Although the change in OKS in different BMI groups is within minimal clinically meaningful difference, it is noteworthy that the differences in absolute OKSs are greater than 4 and remain essentially unchanged after operation.

- 90-day mortality is reported as the outcome of interest, but also 30-day and 60-day mortality are reported in Table 3. Please, select which are the outcomes and at which time points they are analyzed. As it comes to mortality, I understand that 90-day mortality can be considered to represent the risk related to surgery. When weighing the value of surgery, also mortality in longer term is relevant: the benefit of surgery could be interpreted different e.g. if the most obese patients had high 5/10-year mortality. Furthermore, if there are significant differendes in longer-term mortality, it may bias K-M and Cox analyses and one might argue that compering risk analyses should be used instead.

- I do not consider reporting p values necessary when HRs are shown with 95% CI.

- Please replace p=0.0000 with p<0.001 as the p(probability) is hardly zero.

- Supplemental figure 1: There are 252,659 PROMs-HES with unique NJR index numbers, of which ca. 15000 disappear after linkage (there are just 237,288 at the final step). This is not explained or illustrated satisfactorily (a box indicating the faith of these 15000 cases should be added).

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Reviewer #3:

This is a very interesting study of outcomes of TKA for obese patients. It is highly relevant for all the reasons highlighted by the authors. Also outside the UK, we see financially motivated attempts to reduce the number of operations, some of which appear entirely unjustified, e.g. requirements for months of physiotherapy in cases of OA with severe deformity, or refusing private cover for patients with a BMI over 35.

A register is not able to provide answers on causative relations, as the authors correctly argue, and the true effect of a factor on the outcome of a procedure is probably beyond the ability of registers. They are, however, one of the best means of getting information on current practice and current relations between possibly causative (and possibly confounded) factors and outcome. And no better starting point than the largest register.

The results are important, and the consequences of this study are potentially wide-reaching with general effects on health policy.

Does the NJR have information on postoperative weight (and weight loss)? If so, it would be very interesting to have the information included in the analyses.

Introduction

* Very good introduction. Although the aim appears well described, there is some uncertainty, that influences the judgement of appropriateness of the methods used. For instance: is there any time frame for the PRO outcome? Does the study aim to determine PRO improvements in the recovery period or the plateau outcome? Or is this a pragmatic analysis of the available data?

Methods

* Why were patients excluded, if the indication for revision was unknown? Revision is revision, and since indications may be less reliable, I would include all types of revision.

* Why was the analysis restricted to TKR? No interest in unicompartmentals?

* The definition of revision is the well-known triad of removal, addition or exchange. Since a higher infection in obese patients has been suggested, and since some early infections may result in a reoperation not qualifying for a revision, some early complications may have been missed. This should be discussed. There may well be a general need to change focus from revisions to all types of reoperations, even if this deviates from tradition.

* It is not correct to suggest that the OKS covers 12 domains. The questionnaire was developed as a one-domain questionnaire (knee function and pain, not clearly separated), and it resulted in 12 questions within that domain.

* Had the authors had long-time PRO-data, one might argue for not excluding patients after revision. With a 6-month PRO time-frame, the exclusion appears justified.

* The reference to Royston and Parmar should be listed in the references. I am not an expert on the model used, and I would suggest a statistical review of the appropriateness of the model.

* Is BMI data entered directly into the NJR, or is BMI calculated from entries of bodyweight and height? I would expect more errors with the former entry type. Please specify.

* Is there no anchor question in the NJR? Would be very interesting to see this in relation to the OKS improvements instead of a simple reporting of the crude OKS improvements. See comment under Discussion below.

Results

* Comparing the complete and incomplete datasets, the ASA distributions do differ significantly, although possibly similar(?). The same is the case for fixation type. Possible reasons? Consequences? Comments?

* Last 3 lines of Revision paragraph: It should be emphasized, that the 30-35 kg/m2 group did not differ significantly from the normal BMI group. To the casual reader, the message is an 8% higher revision risk, which may not be true.

* First paragraph on OKS: This is just a repetition of table 6. Please provide an interpretation of the data.

Discussion

* A possible limitation is the use of the OKS. The instrument was developed for knee OA patients, but as far as I remember, there was no mentioning of BMI for the focus group patients in the development paper. I also do not remember a validation paper for obese patients. The importance of this is that obese patients may have other needs and expectations, and the quantification of their feelings and function may well be biased by using the same instrument for both groups. As an example, I would assume that obese patients would have far more difficulty in kneeling (question 7) than non-obese patients, but this does not necessarily imply a problem with the surgical outcome. This should be discussed.

* The timing of the post-operative OKS is a certain limitation that should be discussed. By comparing the two groups of patients at a single and identical time point assumes knowledge of identical improvement curves for the groups. It may well be that obese patients recover more slowly than non-obese patients, and the 6-month comparison may give a biased estimate of the "true" difference in outcome between the groups. One group may be measured in the recovery phase, while the other is measured in the plateau phase. This should also be discussed.

Figures

1. It hardly seems necessary to specify reasons for exclusion of no patients.

2. Y-axis should be rescaled to better visualize differences between curves, e.g. range 0-5%.

3. A graphical representation of the uncertainty of the estimate curves would increase the value of this figure. It would be difficult to represent all five, but a cumulated model could be shown.

Nov 10, 2020

Anders Odgaard

Rigshospitalet, Copenhagen University Hospital

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Any attachments provided with reviews can be seen via the following link:

[LINK]

Decision Letter 2

Richard Turner

12 Jun 2021

Dear Dr. Evans,

Thank you very much for re-submitting your manuscript "The effect of obesity on revision surgery, mortality and patient reported outcomes of primary knee replacement surgery: data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man" (PMEDICINE-D-20-04558R2) for consideration at PLOS Medicine.

I have discussed the paper with editorial colleagues and it was also seen again by two reviewers. I am pleased to tell you that, provided the remaining editorial and production issues are fully dealt with, we expect to be able to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

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Please let me know if you have any questions in the meantime, and we look forward to receiving the revised manuscript.   

Sincerely,

Richard Turner, PhD

Senior Editor, PLOS Medicine

rturner@plos.org

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Requests from Editors:

Bearing in mind the observational research design, we ask you to amend the title to better accord with journal style, and suggest: "Obesity and revision surgery, mortality and patient reported outcomes after primary

knee replacement surgery in the National Joint Registry for England, Wales, Northern

Ireland and the Isle of Man: A cohort study".

Please avoid words such as "effect", implying causal inference, throughout the text unless supported by evidence.

In the abstract, to "After adjustment ...", please add a summary of what has been adjusted for.

In the abstract and main text, please quote p values alongside 95% CI, where available.

Please attach the analysis plan as a supplementary document, referred to in your Methods section.

We did not find the RECORD checklist attached - please include this with your revision.

In the checklist, please ensure that individual items are referred to by section (e.g., "Methods") and paragraph number, not by line or page numbers as these generally change in the event of publication.

Please remove the "Role of the funding source" section from the Methods.

Please remove information on funding and competing interests from the end of the main text. In the event of publication, this information will appear in the article metadata, via entries in the submission form.

Throughout the article, please quote exact p values or, for smaller values, p<0.001.

Throughout the text, please style reference call-outs as follows: " ... most patients [1,2]." (noting the space preceding the square bracket and the absence of spaces within the brackets).

Please restrict "world's largest joint registry" to one mention, and add "to our knowledge", or similar.

In the reference list, please use journal name abbreviations (e.g., "Lancet") consistently.

Comments from Reviewers:

*** Reviewer #1:

The authors have addressed my concerns and I now recommend publication

Peter Flom

*** Reviewer #2:

The authors have done thorough work in revising the manuscript according to my and other reviewers' comments. Most importantly, the manuscript is much easier to follow now.

There are just a couple of issues that I'd suggest considering.

1) Supplementary data (S2) now shows number of cases that are still under follow-up at different timepoints. I think this is important information and do not see a reason to "hide" it in the supplementary data. I'd suggest adding the number of cases under follow-up into Figure 2. I may not be necessary to show the numbers for each BMI category. Just the total number could be enough.

2) I think it would be important to show mortality during the follow-up years. In the current analyses regarding prosthesis survival, closure of follow-up and death are dealt with similarly (censoring of the case). As I already commented, mortality is likely different in different BMI groups (and similarly the type of ending the follow-up: closure of follow-up, revision, death) in long-term follow-up and from the viewpoint of considering risks and benefits of surgery, such differences are clinically relevant.

3) Figure 5 shows linear association between preoperative and postoperative OKS scores. The authors have only partly answered to my previous comment. The parts that remained unanswered are: "In its current form its value is questionable and interpretation is difficult: I think it is not that certain that association is linear but instead from lower scores the improvement might be greater." Secondly, there is possibly variation in individual patients' responses and one might hypothesize that variation might be greater in the obese groups. I'd suggest replacing Figure 3 with information based on actual observations (change from pre to postop in different BMI categories and its variation)." I'd like to emphasize that also variation might be of interest. In it's current form, I do not see much value for the current Figure 5.

***

Any attachments provided with reviews can be seen via the following link:

[LINK]

Decision Letter 3

Richard Turner

21 Jun 2021

Dear Dr Evans, 

On behalf of my colleagues and the Academic Editor, Dr Jamsen, I am pleased to inform you that we have agreed to publish your manuscript "Obesity and revision surgery, mortality and patient reported outcomes after primary knee replacement surgery in the National Joint Registry: A cohort study" (PMEDICINE-D-20-04558R3) in PLOS Medicine.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

Prior to final acceptance, we suggest adding "UK" to the title; please also remove the information on funding from the abstract; and convert "p<0.0001" to "p<0.001" in the supplementary tables.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. 

PRESS

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To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper. 

Sincerely, 

Richard Turner, PhD 

Senior Editor, PLOS Medicine

rturner@plos.org

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. STROBE and RECORD checklist.

    RECORD, Reporting of studies Conducted using Observational Routinely-collected Data; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology.

    (DOCX)

    S1 Fig. Flowchart diagram describing the steps to create dataset for PROMs analyses.

    PROMs, Patient Reported Outcome Measures.

    (TIF)

    S2 Fig. Cumulative probability of revision (KM estimates) with at risk table by BMI category.

    BMI, body mass index; KM, Kaplan–Meier.

    (TIF)

    S3 Fig. Cumulative probability of 90-day mortality (KM estimates) with risk table by BMI category.

    BMI, body mass index; KM, Kaplan–Meier.

    (TIF)

    S1 Table. Estimates from the flexible parametric survival model to investigate the association of BMI and revision using the NJR–HES dataset.

    All the models were fitted on the hazard scale using 4 degrees of freedom. Adjusted models adjust for age, gender, type of fixation, ASA grade, year of having the primary operation, indication for operation, IMD, and Charlson comorbidity index. ASA, American Society of Anaesthesiologists; BMI, body mass index; HES, Hospital Episodes Statistics; IMD, Index of Multiple Deprivation; NJR, National Joint Registry; TKR, total knee replacement.

    (DOCX)

    S2 Table. Estimates from the Cox regression model to investigate the association of BMI and mortality within 90 days using the NJR–HES dataset.

    Adjusted models adjusted for age, gender, ASA grade, year of primary TKR, indication for operation, IMD, and Charlson comorbidity index. ASA, American Society of Anaesthesiologists; BMI, body mass index; HES, Hospital Episodes Statistics; IMD, Index of Multiple Deprivation; NJR, National Joint Registry; TKR, total knee replacement.

    (DOCX)

    S3 Table. Coefficients of BMI categories to predict the mean increase or decrease on the postoperative OKS after 6 months.

    Adjusted model adjusts for age, gender, ASA grade, indication for operation, fixation type, and year of receiving the primary TKR, anxiety status, Charlson score, and multiple deprivation index. ASA, American Society of Anaesthesiologists; BMI, body mass index; OKS, Oxford Knee Score; TKR, total knee replacement.

    (DOCX)

    Attachment

    Submitted filename: V1.2_response_to_reviewers.docx

    Attachment

    Submitted filename: V1.0_response_to_reviewers_2.docx

    Data Availability Statement

    Data are available from the NJR research subcommittee researchers who meet the criteria for access to confidential data. Access to the data used in this study can be requested via njrresearch@hqip.org.uk. Full details of how to request NJR data for research can be found at: http://www.njrcentre.org.uk/njrcentre/Research/Research-requests.


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