Publications by authors named "Andrew J Price"

77 Publications

Patient-Reported Function and Quality of Life After Revision Total Knee Arthroplasty: An Analysis of 10,727 Patients from the NHS PROMs Program.

J Arthroplasty 2021 Mar 19. Epub 2021 Mar 19.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford, UK.

Background: The aim of the study was to investigate changes in patient-reported outcome measures (PROMs) after revision total knee arthroplasty (rTKA).

Methods: A total of 10,727 patients undergoing elective rTKA were recruited from the UK National Health Service PROMs data set from 2013 to 2019. PROMs were collected at baseline and six months to assess joint function (Oxford Knee Score, OKS) and quality of life (EQ-5D). Associations with a change in the OKS (COKS) were investigated through multiple linear regression.

Results: The mean COKS was 12.4 (standard deviation 10.7) points. A total of 6776 of 10,329 (65.6%) patients demonstrated increase in the OKS above the minimal important change of 7.5 points. The median change in the EQ-5D utility was 0.227 (interquartile range 0.000 to 0.554). A total of 4917 of 9279 (53.0%) patients achieved a composite endpoint of improvement greater than the minimal important change for joint function and 'better' QoL as per the Paretian analysis. A total of 7477 of 10,727 (69.7%) patients reported satisfaction with rTKA. A total of 7947 of 10,727 (74.1%) patients felt surgery was a success. A total of 4888 of 10,632 (46.0%) patients reported one or more adverse events. A higher preoperative OKS was associated with a lower COKS (coefficient -0.63 [95% confidence interval -0.67 to -0.60]). Other factors associated with a lower COKS were postoperative complication(s), age under 60 years, longer duration of knee problems, patients who identified as disabled, problems in EQ-5D dimensions of anxiety/depression and self-care, comorbid conditions (circulatory problems, diabetes, and depression), and earlier year of procedure in the data set.

Conclusion: Two-thirds of patients experienced a meaningful improvement in joint function after rTKA. However, there was a high frequency of patient-reported complications. These findings may enable better informed discussion of the risks and benefits of discretionary rTKA.
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http://dx.doi.org/10.1016/j.arth.2021.03.037DOI Listing
March 2021

Evidence for the validity of a patient-based instrument for assessment of outcome after revision knee arthroplasty.

Bone Joint J 2021 Apr;103-B(4):627-634

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford, UK.

Aims: To estimate the measurement properties for the Oxford Knee Score (OKS) in patients undergoing revision knee arthroplasty (responsiveness, minimal detectable change (MDC-90), minimal important change (MIC), minimal important difference (MID), internal consistency, construct validity, and interpretability).

Methods: Secondary data analysis was performed for 10,727 patients undergoing revision knee arthroplasty between 2013 to 2019 using a UK national patient-reported outcome measure (PROM) dataset. Outcome data were collected before revision and at six months postoperatively, using the OKS and EuroQol five-dimension score (EQ-5D). Measurement properties were assessed according to COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) guidelines.

Results: A total of 9,219 patients had complete outcome data. Mean preoperative OKS was 16.7 points (SD 8.1), mean postoperative OKS 29.1 (SD 11.4), and mean change in OKS + 12.5 (SD 10.7). Median preoperative EQ-5D index was 0.260 (interquartile range (IQR) 0.055 to 0.691), median postoperative EQ-5D index 0.691 (IQR 0.516 to 0.796), and median change in EQ-5D index + 0.240 (IQR 0.000 to 0.567). Internal consistency was good with Cronbach's α 0.88 (baseline) and 0.94 (post-revision). Construct validity found a high correlation of OKS total score with EQ-5D index ( = 0.76 (baseline), = 0.83 (post-revision), p < 0.001). The OKS was responsive with standardized effect size (SES) 1.54 (95% confidence interval (CI) 1.51 to 1.57), compared to SES 0.83 (0.81 to 0.86) for the EQ-5D index. The MIC for the OKS was 7.5 points (95% CI 5.5 to 8.5) based on the optimal cut-off with specificity 0.72, sensitivity 0.60, and area under the curve 0.66. The MID for the OKS was 5.2 points. The MDC-90 was 3.9 points. The OKS did not demonstrate significant floor or ceiling effects.

Conclusion: This study found that the OKS was a useful and valid instrument for assessment of outcome following revision knee arthroplasty. The OKS was responsive to change and demonstrated good measurement properties. Cite this article:  2021;103-B(4):627-634.
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http://dx.doi.org/10.1302/0301-620X.103B4.BJJ-2020-1560.R1DOI Listing
April 2021

Time to reconsider the routine use of tourniquets in total knee arthroplasty surgery.

Bone Joint J 2021 May 8;103-B(5):830-839. Epub 2021 Mar 8.

Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.

Aims: Many surgeons choose to perform total knee arthroplasty (TKA) surgery with the aid of a tourniquet. A tourniquet is a device that fits around the leg and restricts blood flow to the limb. There is a need to understand whether tourniquets are safe, and if they benefit, or harm, patients. The aim of this study was to determine the benefits and harms of tourniquet use in TKA surgery.

Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, and trial registries up to 26 March 2020. We included randomized controlled trials (RCTs), comparing TKA with a tourniquet versus without a tourniquet. Outcomes included: pain, function, serious adverse events (SAEs), blood loss, implant stability, duration of surgery, and length of hospital stay.

Results: We included 41 RCTs with 2,819 participants. SAEs were significantly more common in the tourniquet group (53/901 vs 26/898, tourniquet vs no tourniquet respectively) (risk ratio 1.73 (95% confidence interval (CI) 1.10 to 2.73). The mean pain score on the first postoperative day was 1.25 points higher (95% CI 0.32 to 2.19) in the tourniquet group. Overall blood loss did not differ between groups (mean difference 8.61 ml; 95% CI -83.76 to 100.97). The mean length of hospital stay was 0.34 days longer in the group that had surgery with a tourniquet (95% CI 0.03 to 0.64) and the mean duration of surgery was 3.7 minutes shorter (95% CI -5.53 to -1.87).

Conclusion: TKA with a tourniquet is associated with an increased risk of SAEs, pain, and a marginally longer hospital stay. The only finding in favour of tourniquet use was a shorter time in theatre. The results make it difficult to justify the routine use of a tourniquet in TKA surgery. Cite this article:  2021;103-B(5):830-839.
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http://dx.doi.org/10.1302/0301-620X.103B.BJJ-2020-1926.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091001PMC
May 2021

Revision knee replacement for prosthetic joint infection: Epidemiology, clinical outcomes and health-economic considerations.

Knee 2021 Jan 23;28:417-421. Epub 2021 Jan 23.

Nuffield Orthopaedic Centre, Windmill Road, Oxford OX2 9JA, UK. Electronic address:

Prosthetic joint infection (PJI) is a devastating complication of knee replacement surgery. Recent evidence has shown that the burden of disease is increasing as more and more knee replacement procedures are performed. The current incidence of revision total knee replacement (TKR) for PJI is estimated at 7.5 cases per 1000 primary joint replacement procedures at 10 years. Revision TKR for PJI is complex surgery, and is associated to a high rate of post-operative complications. The 5-year patient mortality is comparable to some common cancer diagnoses, and more than 15% of patients require re-revision by 10 years. Patient-reported outcome measures (PROMs) including joint function may be worse following revision TKR for PJI than for aseptic indications. The complexity and extended length of the treatment pathway for PJI places a significant burden on the healthcare system, highlighting it as an area for future research to identify the most clinically and cost-effective interventions.
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http://dx.doi.org/10.1016/j.knee.2020.12.024DOI Listing
January 2021

Tourniquet use for knee replacement surgery.

Cochrane Database Syst Rev 2020 12 8;12:CD012874. Epub 2020 Dec 8.

Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.

Background: Many surgeons prefer to perform total knee replacement surgery with the aid of a tourniquet. A tourniquet is an occlusive device that restricts distal blood flow to help create a bloodless field during the procedure. A tourniquet may be associated with increased risk of pain and complications.

Objectives: To determine the benefits and harms of tourniquet use in knee replacement surgery.

Search Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to 26 March 2020. We searched clinicaltrials.gov, the World Health Organization trials portal, and several international registries and joint registries up to March 2020.

Selection Criteria: We included randomised controlled trials (RCTs) comparing knee replacement with use of a tourniquet versus without use of a tourniquet and non-randomised studies with more than 1000 participants. Major outcomes included pain, function, global assessment of success, health-related quality of life, serious adverse events (including venous thromboembolism, infection, re-operation, and mortality), cognitive function, and survival of the implant. Minor outcomes included blood loss, economic outcomes, implant stability, and adverse events.

Data Collection And Analysis: Two review authors screened abstracts and full texts, extracted data, performed risk of bias assessments, and assessed the certainty of the evidence using the GRADE approach.

Main Results: We included 41 RCTs with 2819 participants. Trials included from 20 to 199 participants. Mean age ranged between 58 and 84 years. More than half of the RCTs had unclear risk of selection bias and unclear risk of performance and detection bias due to absence of blinding of participants and surgeons. Major outcomes Pain: at postoperative day 1, pain (on a scale from zero to 10, with higher scores indicating worse pain) was ranked at 4.56 points after surgery without a tourniquet and at 1.25 points (MD) higher (95% CI 0.32 higher to 2.19 higher) with a tourniquet (8 studies; 577 participants), for an absolute difference of 12.5% higher pain scores (95% CI 3.2% higher to 21.9% higher) and a relative difference of 19% higher pain scores (95% CI 3.4% higher to 49% higher) with a tourniquet. Evidence for these findings was of moderate certainty, downgraded due to risk of bias. Knee replacement with a tourniquet probably led to higher postoperative pain scores at day 1, although this difference may or may not be noticeable to patients (based on a minimal clinically important difference (MCID) of 1.0). Function: at 12 months, tourniquet use probably makes little or no difference to function, based on an MCID of 5.3 for Knee Society Score (KSS) and 5.0 for Oxford Knee Score (OKS). Mean function (on a scale from 0 to 100, with higher scores indicating better outcomes) was 90.03 points after surgery without a tourniquet and was 0.29 points worse (95% CI 1.06 worse to 0.48 better) on a 0 to 100 scale, absolute difference was 0.29% worse (1.06% worse to 0.48% better), with a tourniquet (5 studies; 611 participants). This evidence was downgraded to moderate certainty due to risk of bias. Global assessment of success: low-certainty evidence (downgraded due to bias and imprecision) indicates that tourniquet use may have little or no effect on success. At six months, 47 of 50 (or 940 per 1000) reported overall successful treatment after surgery without a tourniquet and 47 of 50 (or 940 per 1000) with a tourniquet (risk ratio (RR) 1.0, 95% CI 0.91 to 1.10) based on one study with 100 participants. Health-related quality of life: at six months, tourniquet may have little or no effect on quality of life. The 12-Item Short Form Survey (SF-12) score (mental component from zero to 100 (100 is best)) was 54.64 after surgery without a tourniquet and 1.53 (MD) better (95% CI 0.85 worse to 3.91 better) with a tourniquet (1 study; 199 participants); absolute difference was 1.53% better (0.85% worse to 3.91% better). Evidence was of low certainty, downgraded due to risk of bias and small number of participants. Serious adverse events: the risk of serious adverse events was probably higher with tourniquet; 26 of 898 (29 per 1000) reported events following surgery without a tourniquet compared to 53 of 901 (59 per 1000) with a tourniquet (RR 1.73, 95% CI 1.10 to 2.73) in 21 studies (1799 participants). Twenty-nine more per 1000 patients (95% CI 3 to 50 more per 1000 patients) had a serious adverse event with a tourniquet. Forty-eight (95% CI 20 to 345) participants would need to have surgery without a tourniquet to avoid one serious adverse event. This evidence was downgraded to moderate certainty due to risk of bias. Cognitive function: one study reported cognitive function as an outcome; however the data were incompletely reported and could not be extracted for analysis. Survival of implant: it is uncertain if tourniquet has an effect on implant survival due to very low certainty evidence (downgraded for bias, and twice due to very low event rates); 2 of 107 (19 per 1000) required revision surgery in the surgery with a tourniquet group compared to 1 of 107 (9 per 1000) without a tourniquet group at up to two years' follow-up (RR 1.44, 95% CI 0.23 to 8.92). This equates to a 0.4% (0.7% lower to 7% more) increased absolute risk in surgery with a tourniquet.

Authors' Conclusions: Moderate certainty evidence shows that knee replacement surgery with a tourniquet is probably associated with an increased risk of serious adverse events. Surgery with a tourniquet is also probably associated with higher postoperative pain, although this difference may or may not be noticeable to patients. Surgery with a tourniquet does not appear to confer any clinically meaningful benefit on function, treatment success or quality of life. Further research is required to explore the effects of tourniquet use on cognitive function and implant survival, to identify any additional harms or benefits. If a tourniquet continues to be used in knee replacement surgery, patients should be informed about the potential increased risk of serious adverse events and postoperative pain.
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http://dx.doi.org/10.1002/14651858.CD012874.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094224PMC
December 2020

Management of aseptic failure of the mobile-bearing Oxford unicompartmental knee arthroplasty.

Knee 2020 Dec 13;27(6):1721-1728. Epub 2020 Nov 13.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford, UK.

Background: Unicompartmental knee arthroplasty (UKA) accounts for 9.1% of primary knee arthroplasties (KAs) in the UK. However, wider uptake is limited by higher revision rates compared with total knee arthroplasties (TKA) and concerns over subsequent poor function. The aim of this study was to understand the revision strategies and clinical outcomes for aseptic, failed UKAs at a high-volume centre.

Methods: This was a retrospective, single-centre cohort study of 48 patients (31 female, 17 male) with 52 revision UKAs from 2006 to 2018. Median time to revision was 67 (range 4-180) months. Indications for revision were progression of osteoarthritis (n = 31 knees, 59.6%), unexplained pain (n = 10 knees, 19.2%), aseptic loosening (n = 6 knees, 11.5%), medial collateral ligament incompetence (n = 3 knees, 5.8%) and recurrent bearing dislocation (n = 2 knees, 3.8%). Technical details of surgery, complications and functional outcome were recorded.

Results: Failed UKAs were revised to primary TKAs (n = 29 knees, 55.8%), revision TKAs (n = 9 knees, 17.3%), bicompartmental KAs (n = 11 knees, 21.2%), or unicompartmental-to-unicompartmental KAs (n = 3 knees, 5.8%). Median follow up was 81 (range 24-164) months. Four patients (7.7%) died from unrelated causes. No re-revisions were identified. Surgical complications required re-operation in five knees (9.6%). Median Oxford Knee Score at latest follow up was 38 (range 9-48) points and median EQ5D3L index 0.707 (range -0.247 to 1.000).

Conclusions: Aseptic, revision UKA at a high-volume centre had good clinical outcomes. Bicompartmental KA demonstrated excellent function and should be considered an alternative to TKA for progression of osteoarthritis for appropriately trained surgeons.
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http://dx.doi.org/10.1016/j.knee.2020.10.003DOI Listing
December 2020

Who gets referred for knee or hip replacement? A theoretical model of the potential impact of evidence-based referral thresholds using data from a retrospective review of clinic records from an English musculoskeletal referral hub.

BMJ Open 2020 07 2;10(7):e028915. Epub 2020 Jul 2.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, Oxfordshire, UK.

Objectives: To estimate the relationship between patient characteristics and referral decisions made by musculoskeletal hubs, and to assess the possible impact of an evidence-based referral tool.

Design: Retrospective analysis of medical records and decision tree model evaluating policy changes using local and national data.

Setting: One musculoskeletal interface clinic (hub) in England.

Participants: 922 adults aged ≥50 years referred by general practitioners with symptoms of knee or hip osteoarthritis.

Interventions: We assessed the current frequency and determinants of referrals from one hub and the change in referrals that would occur at this centre and nationally if evidence-based thresholds for referral (Oxford Knee and Hip Scores, OKS/OHS) were introduced.

Main Outcome Measure: OKS/OHS, referrals for surgical assessment, referrals for arthroplasty, costs and quality-adjusted life years.

Results: Of 110 patients with knee symptoms attending face-to-face hub consultations, 49 (45%) were referred for surgical assessment; the mean OKS for these 49 patients was 18 (range: 1-41). Of 101 hip patients, 36 (36%) were referred for surgical assessment (mean OHS: 21, range: 5-44). No patients referred for surgical assessment were above previously reported economic thresholds for OKS (43) or OHS (45). Setting thresholds of OKS ≤31 and OHS ≤35 might have resulted in an additional 22 knee referrals and 26 hip referrals in our cohort. Extrapolating hub results across England suggests a possible increase in referrals nationally, of around 13 000 additional knee replacements and 4500 additional hip replacements each year.

Conclusions: Musculoskeletal hubs currently consider OKS/OHS and other factors when making decisions about referral to secondary care for joint replacement. Those referred typically have low OHS/OKS, and introducing evidence-based OKS/OHS thresholds would prevent few inappropriate (high-functioning, low-pain) referrals. However, our findings suggest that some patients not currently referred could benefit from arthroplasty based on OKS/OHS. More research is required to explore other important patient characteristics currently influencing hub decisions.
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http://dx.doi.org/10.1136/bmjopen-2019-028915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335627PMC
July 2020

Further reflections on TOPKAT and Partial . Total Knee Replacement-response to authors.

Ann Transl Med 2020 Jun;8(11):730

Health Services Research Unit, Health Sciences Building, University of Aberdeen, Aberdeen, UK.

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http://dx.doi.org/10.21037/atm-2020-59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327336PMC
June 2020

The use of patient-reported outcome measures to guide referral for hip and knee arthroplasty.

Bone Joint J 2020 Jul;102-B(7):941-949

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK.

Aims: To calculate how the likelihood of obtaining measurable benefit from hip or knee arthroplasty varies with preoperative patient-reported scores.

Methods: Existing UK data from 222,933 knee and 209,760 hip arthroplasty patients were used to model an individual's probability of gaining meaningful improvement after surgery based on their preoperative Oxford Knee or Hip Score (OKS/OHS). A clinically meaningful improvement after arthroplasty was defined as ≥ 8 point improvement in OHS, and ≥ 7 in OKS.

Results: The upper preoperative score threshold, above which patients are unlikely to achieve any meaningful improvement from surgery, is 41 for knees and 40 for hips. At lower scores, the probability of improvement increased towards a maximum of 88% (knee) and 95% for (hips).

Conclusion: By our definition of meaningful improvement, patients with preoperative scores above 41 (OKS) and 40 (OHS) should not be routinely referred to secondary care for possible arthroplasty. Using lower thresholds would incrementally increase the probability of meaningful benefit for those referred but will exclude some patients with potential to benefit. The findings are useful to support the complex shared decision-making process in primary care for referral to secondary care; and in secondary care for experienced clinicians counselling patients considering knee or hip arthroplasty, but should not be used in isolation. Cite this article: 2020;102-B(7):941-949.
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http://dx.doi.org/10.1302/0301-620X.102B7.BJJ-2019-0102.R2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376303PMC
July 2020

Manipulation Under Anesthetic After Primary Knee Arthroplasty Is Associated With a Higher Rate of Subsequent Revision Surgery.

J Arthroplasty 2020 09 11;35(9):2640-2645.e2. Epub 2020 Apr 11.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; NIHR Biomedical Research Unit, University of Oxford, Oxford, UK; Nuffield Orthopaedic Centre, Oxford, UK.

Aim: To determine the association between manipulation under anesthetic (MUA) after primary knee arthroplasty and subsequent revision surgery.

Methods: Patients undergoing primary knee arthroplasty from April 2011 to April 2016 with minimum 1-year follow-up to April 2017 were identified from the national hospital episode statistics for England. The first arthroplasty per patient, per side, was included; cases with a record of subsequent infection or periprosthetic fracture were excluded. Patients undergoing MUA within 1 year to the same knee were identified, defining the populations for the MUA and non-MUA cohorts. Mortality-adjusted Kaplan-Meier survival analysis (revision arthroplasty) was performed to a maximum of 6 years. A Cox proportional hazards model was used to determine the hazard for revision, adjusting for type of primary arthroplasty, gender, age group, year, comorbidity index, obesity, regional deprivation, rurality, and ethnicity.

Results: A total of 309,650 primary arthroplasty cases (309,650 patients) were included. MUA within 1 year was recorded in 6882 patients (2.22%; 95% confidence interval [95% CI], 2.17-2.28) defining the MUA cohort; all others were included in the parallel non-MUA cohort. At 6 years, the mortality-adjusted estimated implant survival rate in the MUA cohort was 91.2% (95% CI, 90.0-92.2) in comparison to 98.1% (95% CI, 98.0-98.2) in the non-MUA cohort. In the fully adjusted model, this corresponded to an adjusted hazard for revision of 5.03 (hazard ratio; 95% CI, 4.55-5.57).

Conclusion: Patients who underwent MUA within 1 year of primary arthroplasty were at a 5-fold increased risk of subsequent revision even after excluding cases of infection or fracture. Further investigation of the etiology of stiffness after primary knee arthroplasty and the optimal treatment options to improve outcomes is justified.
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http://dx.doi.org/10.1016/j.arth.2020.04.015DOI Listing
September 2020

Rates of knee arthroplasty in patients with a history of arthroscopic chondroplasty: results from a retrospective cohort study utilising the National Hospital Episode Statistics for England.

BMJ Open 2020 04 16;10(4):e030609. Epub 2020 Apr 16.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objective: The purpose of this study was to analyse the rate of knee arthroplasty in the population of patients with a history of arthroscopic chondroplasty of the knee, in England, over 10 years, with comparison to general population data for patients without a history of chondroplasty.

Design: Retrospective cohort study.

Setting: English Hospital Episode Statistics (HES) data.

Participants And Interventions: Patients undergoing arthroscopic chondroplasty in England between 2007/2008 and 2016/2017 were identified. Patients undergoing previous arthroscopic knee surgery or simultaneous cruciate ligament reconstruction or microfracture in the same knee were excluded.

Outcomes: Patients subsequently undergoing a knee arthroplasty in the same knee were identified and mortality-adjusted survival analysis was performed (survival without undergoing knee arthroplasty). A Cox proportional hazards model was used to identify factors associated with knee arthroplasty. Relative risk of knee arthroplasty (total or partial) in comparison to the general population was determined.

Results: Through 2007 to 2017, 157 730 eligible chondroplasty patients were identified. Within 1 year, 5.91% (7984/135 197; 95% CI 5.78 to 6.03) underwent knee arthroplasty and 14.22% (8145/57 267; 95% CI 13.94 to 14.51) within 5 years. Patients aged over 30 years with a history of chondroplasty were 17.32 times (risk ratio; 95% CI 16.81 to 17.84) more likely to undergo arthroplasty than the general population without a history of chondroplasty.

Conclusions: Patients with cartilage lesions of the knee, treated with arthroscopic chondroplasty, are at greater risk of subsequent knee arthroplasty than the general population and for a proportion of patients, there is insufficient benefit to prevent the need for knee arthroplasty within 1 to 5 years. These important new data will inform patients of the anticipated outcomes following this procedure. The risk in comparison to non-operative treatment remains unknown and there is an urgent need for a randomised clinical trial in this population.
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http://dx.doi.org/10.1136/bmjopen-2019-030609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200031PMC
April 2020

Demographic and geographical variability in physiotherapy provision following hip and knee replacement. An analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

Physiotherapy 2020 03 20;106:1-11. Epub 2019 Nov 20.

Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

Background: Total hip (THR) and knee replacement (TKR) are two of the most common elective orthopaedic procedures worldwide. Physiotherapy is core to the recovery of people following joint replacement. However, there remains uncertainty as to physiotherapy provision at a national level.

Objectives: To examine the relationship between patient impairment and geographical variation on the provision of physiotherapy among patients who undergo primary total hip or knee replacement (THR/TKR).

Design: Population-based observational cohort study.

Methods: Patients undergoing THR (n=17,338) or TKR (n=20,260) recorded in the National Joint Registry for England (NJR) between 2009 and 2010 and completed Patient Reported Outcome Measures (PROMs) questionnaires at Baseline and 12 months postoperatively. Data were analysed on the frequency of physiotherapy over the first postoperative year across England's Strategic Health Authorities (SHAs). Logistic regression analyses examined the relationship between a range of patient and geographical characteristics and physiotherapy provision.

Results: Following THR, patients were less likely to receive physiotherapy than following TKR patients ('some' treatment by a physiotherapist within 1st post operative year: 53% vs 79%). People with worse functional outcomes 12 months postoperatively, received more physiotherapy after THR and TKR. There was substantial variation in provision of physiotherapy according to age (younger people received more physiotherapy), gender (females received more physiotherapy) ethnicity (non-whites received more physiotherapy) and geographical location (40% of patients from South West received some physiotherapy compared to 40 73% in London after THR).

Conclusions: There is substantial variation in the provision of physiotherapy nationally. This variation is not explained by differences in the patient's clinical presentation.
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http://dx.doi.org/10.1016/j.physio.2019.11.003DOI Listing
March 2020

Varus alignment of the proximal tibia is associated with structural progression in early to moderate varus osteoarthritis of the knee.

Knee Surg Sports Traumatol Arthrosc 2020 Oct 21;28(10):3279-3286. Epub 2020 Jan 21.

Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Rd, Oxford, OX3 7LD, UK.

Purpose: Lower limb malalignment is a strong predictor of progression in knee osteoarthritis. The purpose of this study is to identify the individual alignment variables that predict progression in early to moderate osteoarthritis of the knee.

Method: A longitudinal cohort study using data from the Osteoarthritis Initiative. In total, 955 individuals (1329 knees) with early to moderate osteoarthritis (Kellgren-Lawrence grade 1, 2 or 3) were identified. All subjects had full-limb radiographs analysed using the Osteotomy module within Medicad Classic (Hectec GMBH) to give a series of individual alignment variables relevant to the coronal alignment of the lower limb. Logistic regression models, with generalised estimating equations were used to identify which of these individual alignment variables predict symptom worsening (WOMAC score > 9 points) and or structural progression (joint space narrowing progression in the medial compartment > 0.7mm) over 24 months.

Results: Individual alignment variable were associated with both valgus and varus alignment (mechanical Lateral Distal Femoral Angle, Medial Proximal Tibial Angle and mechanical Lateral Distal Tibial Angle). Only the Medial Proximal Tibial Angle was significantly associated with structural progression and none of the variables was associated with symptom progression. The odds of joint space narrowing progression in the medial compartment occurring at 24 months increased by 21% for every one degree decrease (more varus) in Medial Proximal Tibial Angle (p < 0.001) CONCLUSIONS: Our results suggest that the risk of structural progression in the medial compartment is associated with greater varus alignment of the proximal tibia.

Level Of Evidence: Level III, retrospective cohort study.
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http://dx.doi.org/10.1007/s00167-019-05840-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511471PMC
October 2020

Mortality and adverse joint outcomes following septic arthritis of the native knee: a longitudinal cohort study of patients receiving arthroscopic washout.

Lancet Infect Dis 2020 03 17;20(3):341-349. Epub 2019 Dec 17.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK; National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK.

Background: The short-term and long-term consequences of septic arthritis are uncertain. We aimed to determine risk of mortality and adverse joint outcomes following septic arthritis of the native knee.

Methods: We did a retrospective cohort study in patients who received arthroscopic knee washout for septic arthritis in England between April 1, 1997, and March 31, 2017, using data in the national Hospital Episode Statistics database. Patients with previous knee surgery to the same knee were excluded. Mortality within 90 days, adverse joint outcomes (arthrodesis, amputation, arthroplasty) within 1 year, and arthroplasty within 15 years were determined. Mortality in patients with a primary admitting diagnosis of septic arthritis (ICD-10) was compared with that in patients in whom septic arthritis was a secondary diagnosis.

Findings: 12 132 patients were included (mean age 56·6 years [SD 24·9]) of whom 4307 (36%) were female. In 10 195 (84%) patients with septic arthritis as the primary admitting diagnosis, 90-day mortality was 7·05% (95% CI 6·56-7·57; 719 patients), rising to 22·69% (20·80-24·68; 418 patients) in 1842 patients older than 79 years. Secondary septic arthritis diagnosis versus primary diagnosis was associated with an adjusted odds ratio for mortality of 2·10 (95% CI 1·79-2·46; p<0·0001). In 11 393 patients with at least 1 year follow-up, the 1 year rates were 0·13% (95% CI 0·07-0·22; 15 patients) for arthrodesis, 0·40% (0·30-0·54; 46 patients) for amputation, and 1·33%; (1·13-1·56; 152 patients) for arthroplasty. Within 15 years, 159 (8·76%; 95% CI 7·50-10·15) of 1816 patients had received arthroplasty, corresponding to an annual risk of arthroplasty that was about six times that of the general population (risk ratio 6·14, 95% CI 4·95-7·62; p<0·0001).

Interpretation: The consequences of septic knee arthritis in patients undergoing arthroscopic knee washout are serious. These findings highlight the potentially devastating outcomes associated with sepsis from musculoskeletal joint infection.

Funding: National Institute for Health Research.
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http://dx.doi.org/10.1016/S1473-3099(19)30419-0DOI Listing
March 2020

Hdac3, Setdb1, and Kap1 mark H3K9me3/H3K14ac bivalent regions in young and aged liver.

Aging Cell 2020 02 19;19(2):e13092. Epub 2019 Dec 19.

Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.

Post-translational modifications of histone tails play a crucial role in gene regulation. Here, we performed chromatin profiling by quantitative targeted mass spectrometry to assess all possible modifications of the core histones. We identified a bivalent combination, a dually marked H3K9me3/H3K14ac modification in the liver, that is significantly decreased in old hepatocytes. Subsequent sequential ChIP-Seq identified dually marked single nucleosome regions, with reduced number of sites and decreased signal in old livers, confirming mass spectrometry results. We detected H3K9me3 and H3K14ac bulk ChIP-Seq signal in reChIP nucleosome regions, suggesting a correlation between H3K9me3/H3K14ac bulk bivalent genomic regions and dually marked single nucleosomes. Histone H3K9 deacetylase Hdac3, as well as H3K9 methyltransferase Setdb1, found in complex Kap1, occupied both bulk and single nucleosome bivalent regions in both young and old livers, correlating to presence of H3K9me3. Expression of genes associated with bivalent regions in young liver, including those regulating cholesterol secretion and triglyceride synthesis, is upregulated in old liver once the bivalency is lost. Hence, H3K9me3/H3K14ac dually marked regions define a poised inactive state that is resolved with loss of one or both of the chromatin marks, which subsequently leads to change in gene expression.
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http://dx.doi.org/10.1111/acel.13092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996956PMC
February 2020

Long-term rates of knee arthroplasty in a cohort of 834 393 patients with a history of arthroscopic partial meniscectomy.

Bone Joint J 2019 Sep;101-B(9):1071-1080

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Aims: The aim of this study was to determine the long-term risk of undergoing knee arthroplasty in a cohort of patients with meniscal tears who had undergone arthroscopic partial meniscectomy (APM).

Patients And Methods: A retrospective national cohort of patients with a history of isolated APM was identified over a 20-year period. Patients with prior surgery to the same knee were excluded. The primary outcome was knee arthroplasty. Hazard ratios (HRs) were adjusted by patient age, sex, year of APM, Charlson comorbidity index, regional deprivation, rurality, and ethnicity. Risk of arthroplasty in the index knee was compared with the patient's contralateral knee (with without a history of APM). A total of 834 393 patients were included (mean age 50 years; 37% female).

Results: Of those with at least 15 years of follow-up, 13.49% (16 256/120 493; 95% confidence interval (CI) 13.30 to 13.69) underwent subsequent arthroplasty within this time. In women, 22.07% (95% CI 21.64 to 22.51) underwent arthroplasty within 15 years compared with 9.91% of men (95% CI 9.71 to 10.12), corresponding to a risk ratio (RR) of 2.23 (95% CI 2.16 to 2.29). Relative to the general population, patients with a history of APM were over ten times more likely (RR 10.27; 95% CI 10.07 to 10.47) to undergo arthroplasty rising to almost 40 times more likely (RR 39.62; 95% CI 27.68 to 56.70) at a younger age (30 to 39 years). In patients with a history of APM in only one knee, the risk of arthroplasty in that knee was greatly elevated in comparison with the contralateral knee (no APM; HR 2.99; 95% CI 2.95 to 3.02).

Conclusion: Patients developing a meniscal tear undergoing APM are at greater risk of knee arthroplasty than the general population. This risk is three-times greater in the patient's affected knee than in the contralateral knee. Women in the cohort were at double the risk of progressing to knee arthroplasty compared with men. These important new reference data will inform shared decision making and enhance approaches to treatment, prevention, and clinical surveillance. Cite this article: 2019;101-B:1071-1080.
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http://dx.doi.org/10.1302/0301-620X.101B9.BJJ-2019-0335.R1DOI Listing
September 2019

Rates of Adverse Outcomes and Revision Surgery After Anterior Cruciate Ligament Reconstruction: A Study of 104,255 Procedures Using the National Hospital Episode Statistics Database for England, UK.

Am J Sports Med 2019 09 26;47(11):2533-2542. Epub 2019 Jul 26.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: After an anterior cruciate ligament (ACL) injury, ACL reconstruction is an elective procedure, and therefore, an understanding of the attributable risk from undergoing ACL reconstruction is necessary for patients to make a fully informed treatment decision.

Purpose: To determine the absolute risk of adverse outcomes including reoperation after ACL reconstruction with comparison, where possible, to the rate of adverse events reported in the general population.

Study Design: Descriptive epidemiology study.

Methods: National hospital data on all ACL reconstructions performed in England between April 1, 1997, and March 31, 2017, were analyzed. Revision cases, bilateral procedures within 6 months, and cases with concurrent cartilage or multiple ligament surgery were excluded. The primary outcome was the occurrence of at least 1 serious complication (myocardial infarction, stroke, pulmonary embolism, infection requiring surgery, fasciotomy, neurovascular injury, or death) within 90 days. Additionally, 5-year rates of revision ACL reconstruction, contralateral ACL reconstruction, and meniscal surgery were investigated.

Results: There were 133,270 ACL reconstructions performed, of which 104,255 were eligible for analysis. Within 90 days, serious complications occurred in 675 (0.65% [95% CI, 0.60-0.70]), including 494 reoperations for infections (0.47% [95% CI, 0.43-0.52]) and 129 for pulmonary embolism (0.12% [95% CI, 0.10-0.15]). Of 54,275 procedures with at least 5 years' follow-up, 1746 (3.22% [95% CI, 3.07-3.37]) underwent revision ACL reconstruction in the same knee, 1553 underwent contralateral ACL reconstruction (2.86% [95% CI, 2.72-3.01]), and 340 underwent meniscal surgery (0.63% [95% CI, 0.56-0.70]). The overall risk of serious complications fell over time (adjusted odds ratio [OR], 0.96 per year [95% CI, 0.95-0.98]); however, older patients (adjusted OR, 1.11 per 5 years [95% CI, 1.07-1.16]) and patients with a greater modified Charlson Comorbidity Index (adjusted OR, 2.41 per 10 units [95% CI, 1.65-3.51]) were at a higher risk. For every 850 (95% CI, 720-1039) ACL reconstructions, 1 pulmonary embolism could be provoked. For every 213 (95% CI, 195-233), 1 native knee joint infection could be provoked.

Conclusion: The overall risk of adverse events after ACL reconstruction is low; however, some rare but serious complications, including infections or pulmonary embolism, may occur. Around 3% of patients undergo further ipsilateral or contralateral ACL reconstruction within 5 years. These data will inform shared decision making between clinicians and patients considering their treatment options.
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http://dx.doi.org/10.1177/0363546519861393DOI Listing
September 2019

Surgical interventions for symptomatic mild to moderate knee osteoarthritis.

Cochrane Database Syst Rev 2019 07 19;7:CD012128. Epub 2019 Jul 19.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, Oxford, UK, OX3 7LD.

Background: Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss, bony erosion, and deformity. Many studies do not stratify their results based on the severity of the disease at baseline or recruitment.

Objectives: To assess the benefits and harms of surgical intervention for the management of symptomatic mild to moderate knee osteoarthritis defined as knee pain and radiographic evidence of non-end stage osteoarthritis (Kellgren-Lawrence grade 1, 2, 3 or equivalent on MRI/arthroscopy). Outcomes of interest included pain, function, radiographic progression, quality of life, short-term serious adverse events, re-operation rates and withdrawals due to adverse events.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to May 2018. We also conducted searches of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. Authors of trials were contacted if some but not all their participants appeared to fit our inclusion criteria.

Selection Criteria: We included randomised controlled trials that compared surgery to non-surgical interventions (including sham and placebo control groups, exercise or physiotherapy, and analgesic or other medication), injectable therapies, and trials that compared one type of surgical intervention to another surgical intervention in people with symptomatic mild to moderate knee osteoarthritis.

Data Collection And Analysis: Two review authors independently selected trials and extracted data using standardised forms. We analysed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.

Main Results: A total of five studies involving 566 participants were identified as eligible for this review. Single studies compared arthroscopic partial meniscectomy to physical therapy (320 participants), arthroscopic surgery (debridement ± synovectomy ± chondroplasty) to closed needle joint lavage with saline (32 participants) and high tibial osteotomy surgery to knee joint distraction surgery (62 participants). Two studies (152 participants) compared arthroscopic surgery (washout ± debridement; debridement) to a hyaluronic acid injection. Only one study was at low risk of selection bias, and due to the difficulty of blinding participants to their treatment, all studies were at risk of performance and detection bias.Reporting of results in this summary has been restricted to the primary comparison: surgical intervention versus non-surgical intervention.A single study, included 320 participants with symptoms consistent with meniscal tear. All subjects had the meniscal tear confirmed on knee MRI and radiographic evidence of mild to moderate osteoarthritis (osteophytes, cartilage defect or joint space narrowing). Patients with severe osteoarthritis (KL grade 4) were excluded. The study compared arthroscopic partial meniscectomy and physical therapy to physical therapy alone (a six-week individualised progressive home exercise program). This study was at low risk of selection bias and outcome reporting biases, but was susceptible to performance and detection biases. A high rate of cross-over (30.2%) occurred from the physical therapy group to the arthroscopic group.Low-quality evidence suggests there may be little difference in pain and function at 12 months follow-up in people who have arthroscopic partial meniscectomy and those who have physical therapy. Evidence was downgraded to low quality due to risk of bias and imprecision.Mean pain was 19.3 points on a 0 to 100 point KOOS pain scale with physical therapy at 12 months follow-up and was 0.2 points better with surgery (95% confidence interval (CI) 4.05 better to 3.65 points worse with surgery, an absolute improvement of 0.2% (95% CI 4% better to 4% worse) and relative improvement 0.4% (95% CI 9% better to 8% worse) (low quality evidence). Mean function was 14.5 on a 0 to 100 point KOOS function scale with physical therapy at 12 months follow-up and 0.8 points better with surgery (95% CI 4.3 better to 2.7 worse); 0.8% absolute improvement (95% CI 4% better to 3% worse) and 2.1% relative improvement (95% CI 11% better to 7% worse) (low quality evidence).Radiographic structural osteoarthritis progression and quality of life outcomes were not reported.Due to very low quality evidence, we are uncertain if surgery is associated with an increased risk of serious adverse events, incidence of total knee replacement or withdrawal rates. Evidence was downgraded twice due to very low event rates, and once for risk of bias.At 12 months, the surgery group had a total of three serious adverse events including fatal pulmonary embolism, myocardial infarction and hypoxaemia. The physical therapy alone group had two serious adverse events including sudden death and stroke (Peto OR 1.58, 95% CI 0.27 to 9.21); 1% more events with surgery (95% CI 2% less to 3% more) and 58% relative change (95% CI 73% less to 821% more). One participant in each group withdrew due to adverse events.Two of 164 participants (1.2%) in the physical therapy group and three of 156 in the surgery group underwent conversion to total knee replacement within 12 months (Peto OR 1.76, 95% CI 0.43 to 7.13); 1% more events with surgery (95% CI 2% less to 5% more); 76% relative change (95% CI 57% less to 613% more).

Authors' Conclusions: The review found no placebo-or sham-controlled trials of surgery in participants with symptomatic mild to moderate knee osteoarthritis. There was low quality evidence that there may be no evidence of a difference between arthroscopic partial meniscectomy surgery and a home exercise program for the treatment of this condition. Similarly, low-quality evidence from a few small trials indicates there may not be any benefit of arthroscopic surgery over other non-surgical treatments including saline irrigation and hyaluronic acid injection, or one type of surgery over another. We are uncertain of the risk of adverse events or of progressing to total knee replacement due to very small event rates. Thus, there is uncertainty around the current evidence to support or oppose the use of surgery in mild to moderate knee osteoarthritis. As no benefit has been demonstrated from the low quality trials included in this review, it is possible that future higher quality trials for these surgical interventions may not contradict these results.
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http://dx.doi.org/10.1002/14651858.CD012128.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639936PMC
July 2019

Accuracy of a New Robotically Assisted Technique for Total Knee Arthroplasty: A Cadaveric Study.

J Arthroplasty 2019 11 26;34(11):2799-2803. Epub 2019 Jun 26.

Adult Reconstructive Surgery, Mayo Clinic, Phoenix, AZ.

Background: Although the utility of robotic surgery has already been proven in cadaveric studies, it is our hypothesis that this newly designed robotically assisted system will achieve a high level of accuracy for bone resection. Therefore, we aimed to analyze in a cadaveric study the accuracy to achieve targeted angles and resection thickness.

Methods: For this study, 15 frozen cadaveric specimens (30 knees) were used. In this study, Zimmer Biomet (Warsaw, IN) knees, navigation system, and robot (ROSA Knee System; Zimmer Biomet) were used. Eight trained, board-certified orthopedic surgeons performed robotically assisted total knee arthroplasty implantation using the same robotic protocol with 3 different implant designs. The target angles obtained from the intraoperative planning were then compared to the angles of the bone cuts performed using the robotic system and measured with the computer-assisted system considered to be the gold standard. For each bone cut the resection thickness was measured 3 times by 2 different observers and compared to the values for the planned resections.

Results: All angle mean differences were below 1° and standard deviations below 1°. For all 6 angles, the mean differences between the target angle and the measured values were not significantly different from 0 except for the femoral flexion angle which had a mean difference of 0.95°. The mean hip-knee-ankle axis difference was -0.03° ± 0.87°. All resection mean differences were below 0.7 mm and standard deviations below 1.1mm.

Conclusion: Despite the fact that this study was funded by Zimmer Biomet and only used Zimmer Biomet implants, robot, and navigation tools, the results of our in vitro study demonstrated that surgeons using this new surgical robot in total knee arthroplasty can perform highly accurate bone cuts to achieve the planned angles and resection thickness as measured using conventional navigation.
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http://dx.doi.org/10.1016/j.arth.2019.06.040DOI Listing
November 2019

Rates of knee arthroplasty in anterior cruciate ligament reconstructed patients: a longitudinal cohort study of 111,212 procedures over 20 years.

Acta Orthop 2019 12 10;90(6):568-574. Epub 2019 Jul 10.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK.

Background and purpose - Long-term rates of knee arthroplasty in patients with anterior cruciate ligament (ACL) injury who undergo ligament reconstruction (ACLr) are unclear. We determined this risk of arthroplasty through comparison with the general population.Patients and methods - All patients undergoing an ACLr in England, 1997-2017, were identified from national hospital statistics. Patients subsequently undergoing a knee arthroplasty were identified and survival analysis was performed (survival without undergoing knee arthroplasty). A Cox proportional hazards model was used to identify factors associated with knee arthroplasty. Relative risk of knee arthroplasty (total or partial) in comparison with the general population was determined.Results - 111,212 ACLr patients were eligible for analysis (mean age 29; 77% male). Overall, 0.46% (95% confidence interval [CI] 0.40-0.52) ACLr patients underwent knee arthroplasty within 5 years, 0.97% (CI 0.82-1.2) within 10 years, and 1.8% (CI 1.4-2.3) within 15 years. Knee arthroplasty risk was greater in older age groups and women. In comparison with the general population, the relative risk of undergoing arthroplasty at a younger age (at time of arthroplasty) was elevated: at 30-39 years (risk ratio [RR] 20; CI 11-35), 40-49 years (RR 7.5; CI 5.5-10), and 50-59 years (RR 2.5; CI 1.8-3.5), but not 60-69 years (RR 1.7; CI 0.93-3.2).Interpretation - Patients sustaining an ACL injury who undergo ACLr are at elevated risk of subsequent knee arthroplasty in comparison with the general population. Although the absolute rate of arthroplasty is low, the risk of arthroplasty at a younger age is particularly elevated. When the outcome of shared decision-making is ACLr, this data will help inform patients and clinicians about the long-term risk of requiring knee arthroplasty.
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http://dx.doi.org/10.1080/17453674.2019.1639360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844427PMC
December 2019

Evidence update: A summary of new evidence to inform treatment decisions for patients with meniscal lesions.

Knee 2019 06 23;26(3):521-523. Epub 2019 May 23.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK; National Institute for Health Research (NIHR), Biomedical Research Centre, Oxford, UK.

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http://dx.doi.org/10.1016/j.knee.2019.04.017DOI Listing
June 2019

Arthroscopic partial meniscectomy for meniscal tears of the knee: a systematic review and meta-analysis.

Br J Sports Med 2020 Jun 22;54(11):652-663. Epub 2019 Feb 22.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objective: To assess the benefit of arthroscopic partial meniscectomy (APM) in adults with a meniscal tear and knee pain in three defined populations (taking account of the comparison intervention): (A) all patients (any type of meniscal tear with or without radiographic osteoarthritis); (B) patients with any type of meniscal tear in a non-osteoarthritic knee; and (C) patients with an unstable meniscal tear in a non-osteoarthritic knee.

Design: Systematic review and meta-analysis.

Datasources: A search of MEDLINE, Embase, CENTRAL, Scopus, Web of Science, Clinicaltrials.gov and ISRCTN was performed, unlimited by language or publication date (inception to 18 October 2018).

Eligibilitycriteria: Randomised controlled trials performed in adults with meniscal tears, comparing APM versus (1) non-surgical intervention; (2) pharmacological intervention; (3) surgical intervention; and (4) no intervention.

Results: Ten trials were identified: seven compared with non-surgery, one pharmacological and two surgical. Findings were limited by small sample size, small number of trials and cross-over of participants to APM from comparator interventions. In group A (all patients) receiving APM versus non-surgical intervention (physiotherapy), at 6-12 months, there was a small mean improvement in knee pain (standardised mean difference [SMD] 0.22 [95% CI 0.03 to 0.40]; five trials, 943 patients; I 48%; Grading of Recommendations Assessment, Development and Evaluation [GRADE]: low), knee-specific quality of life (SMD 0.43 [95% CI 0.10 to 0.75]; three trials, 350 patients; I 56%; GRADE: low) and knee function (SMD 0.18 [95% CI 0.04 to 0.33]; six trials, 1050 patients; I 27%; GRADE: low). When the analysis was restricted to people without osteoarthritis (group B), there was a small to moderate improvement in knee pain (SMD 0.35 [95% CI 0.04 to 0.66]; three trials, 402 patients; I 58%; GRADE: very low), knee-specific quality of life (SMD 0.59 [95% CI 0.11 to 1.07]; two trials, 244 patients; I 71%; GRADE: low) and knee function (SMD 0.30 [95% CI 0.06 to 0.53]; four trials, 507 patients; I 44%; GRADE: very low). There was no improvement in knee pain, function or quality of life in patients receiving APM compared with placebo surgery at 6-12 months in group A or B (pain: SMD 0.08 [95% CI -0.24 to 0.41]; one trial, 146 patients; GRADE: low; function: SMD -0.08 [95% CI -0.41 to 0.24]; one trial, 146 patients; GRADE: high; quality of life: SMD 0.05 [95% CI -0.27 to 0.38]; one trial; 146 patients; GRADE: high). No trials were identified for people in group C.

Conclusion: Performing APM in all patients with knee pain and a meniscal tear is not appropriate, and surgical treatment should not be considered the first-line intervention. There may, however, be a small-to-moderate benefit from APM compared with physiotherapy for patients without osteoarthritis. No trial has been limited to patients failing non-operative treatment or patients with an unstable meniscal tear in a non-arthritic joint; research is needed to establish the value of APM in this population.

Protocol Registration Number: PROSPERO CRD42017056844.
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http://dx.doi.org/10.1136/bjsports-2018-100223DOI Listing
June 2020

Patient relevant outcomes of unicompartmental versus total knee replacement: systematic review and meta-analysis.

BMJ 2019 Feb 21;364:l352. Epub 2019 Feb 21.

University of Oxford, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, BOTNAR Research Centre, Headington, Oxford OX3 7LD, UK.

Objective: To present a clear and comprehensive summary of the published data on unicompartmental knee replacement (UKA) or total knee replacement (TKA), comparing domains of outcome that have been shown to be important to patients and clinicians to allow informed decision making.

Design: Systematic review using data from randomised controlled trials, nationwide databases or joint registries, and large cohort studies.

Data Sources: Medline, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Clinical Trials.gov, searched between 1 January 1997 and 31 December 2018.

Eligibility Criteria For Selecting Studies: Studies published in the past 20 years, comparing outcomes of primary UKA with TKA in adult patients. Studies were excluded if they involved fewer than 50 participants, or if translation into English was not available.

Results: 60 eligible studies were separated into three methodological groups: seven publications from six randomised controlled trials, 17 national joint registries and national database studies, and 36 cohort studies. Results for each domain of outcome varied depending on the level of data, and findings were not always significant. Analysis of the three groups of studies showed significantly shorter hospital stays after UKA than after TKA (-1.20 days (95% confidence interval -1.67 to -0.73), -1.43 (-1.53 to -1.33), and -1.73 (-2.30 to -1.16), respectively). There was no significant difference in pain, based on patient reported outcome measures (PROMs), but significantly better functional PROM scores for UKA than for TKA in both non-trial groups (mean difference -0.58 (-0.88 to -0.27) and -0.32 (-0.48 to -0.15), respectively). Regarding major complications, trials and cohort studies had non-significant results, but mortality after TKA was significantly higher in registry and large database studies (risk ratio 0.27 (0.16 to 0.45)), as were venous thromboembolic events (0.39 (0.27 to 0.57)) and major cardiac events (0.22 (0.06 to 0.86)). Early reoperation for any reason was higher after TKA than after UKA, but revision rates at five years remained higher for UKA in all three study groups (risk ratio 5.95 (1.29 to 27.59), 2.50 (1.77 to 3.54), and 3.13 (1.89 to 5.17), respectively).

Conclusions: TKA and UKA are both viable options for the treatment of isolated unicompartmental osteoarthritis. By directly comparing the two treatments, this study demonstrates better results for UKA in several outcome domains. However, the risk of revision surgery was lower for TKA. This information should be available to patients as part of the shared decision making process in choosing treatment options.

Systematic Review Registration: PROSPERO number CRD42018089972.
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http://dx.doi.org/10.1136/bmj.l352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383371PMC
February 2019

Anterior cruciate ligament (ACL) reconstruction and meniscal repair rates have both increased in the past 20 years in England: hospital statistics from 1997 to 2017.

Br J Sports Med 2020 Mar 19;54(5):286-291. Epub 2019 Jan 19.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objectives: We investigated the temporal trend and the geographical variation in the rate of an anterior cruciate ligament (ACL) reconstruction and meniscal repair (MR) performed in England during a 20-year window.

Methods: All hospital episodes for patients undergoing ACL reconstruction or MR between 1 April 1997 and 31 March 2017 were extracted by procedure code from the national hospital episode statistics. Age-standardised and sex-standardised rates of surgery were calculated using Office for National Statistics population data as the denominator and analysed over time both nationally and regionally by National Health Service clinical commissioning group (CCG).

Results: Between 1997-1998 and 2016-2017, there were 133 270 cases of ACL reconstruction (124 489 patients) and 42 651 cases of MR (41 120 patients) (isolated or simultaneous). Nationally, the rate of ACL reconstruction increased 12-fold from 2.0/100K population (95% CI 1.9 to 2.1) in 1997-1998 to 24.2/100K (95% CI 23.8 to 24.6) in 2016-2017. The rate of MR increased more than twofold from 3.0/100K (95% CI 2.8 to 3.1) in 1997-1998 to 7.3/100K (95% CI 7.1 to 7.5) in 2016-2017. Of these cases, the rate of simultaneous ACL reconstruction and MR was 2.6/100K (95% CI 2.5 to 2.8) in 2016/2017. In 2016-2017, for patients aged 20-29, the sex-standardised rate of ACL reconstruction was 76.9/100K (95% CI 74.9 to 78.9) and for MR was 19.8/100K (95% CI 18.8 to 20.9). Practice varied by region-in 2016-2017, 14.5% (30/207) of the CCGs performed more than twice the national average rate of ACL reconstruction and 15.0% (31/207) performed more than twice the national average rate of MR.

Conclusions: The rate of ACL reconstruction (12-fold) and MR (2.4-fold) has increased in England over the last two decades. There is variation in these rates across geographical regions and further work is required to deliver standardised treatment guidance for appropriate use.
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http://dx.doi.org/10.1136/bjsports-2018-100195DOI Listing
March 2020

Mechanical loading of desmosomes depends on the magnitude and orientation of external stress.

Nat Commun 2018 12 11;9(1):5284. Epub 2018 Dec 11.

Group of Molecular Mechanotransduction, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.

Desmosomes are intercellular adhesion complexes that connect the intermediate filament cytoskeletons of neighboring cells, and are essential for the mechanical integrity of mammalian tissues. Mutations in desmosomal proteins cause severe human pathologies including epithelial blistering and heart muscle dysfunction. However, direct evidence for their load-bearing nature is lacking. Here we develop Förster resonance energy transfer (FRET)-based tension sensors to measure the forces experienced by desmoplakin, an obligate desmosomal protein that links the desmosomal plaque to intermediate filaments. Our experiments reveal that desmoplakin does not experience significant tension under most conditions, but instead becomes mechanically loaded when cells are exposed to external mechanical stresses. Stress-induced loading of desmoplakin is transient and sensitive to the magnitude and orientation of the applied tissue deformation, consistent with a stress absorbing function for desmosomes that is distinct from previously analyzed cell adhesion complexes.
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http://dx.doi.org/10.1038/s41467-018-07523-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290003PMC
December 2018

Knee replacement.

Lancet 2018 11;392(10158):1672-1682

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, Nuffield Orthopaedic Centre, Oxford, UK.

Knee replacement surgery is one of the most commonly done and cost-effective musculoskeletal surgical procedures. The numbers of cases done continue to grow worldwide, with substantial variation in utilisation rates across regions and countries. The main indication for surgery remains painful knee osteoarthritis with reduced function and quality of life. The threshold for intervention is not well defined, and is influenced by many factors including patient and surgeon preference. Most patients have a very good clinical outcome after knee replacement, but multiple studies have reported that 20% or more of patients do not. So despite excellent long-term survivorship, more work is required to enhance this procedure and development is rightly focused on increasing the proportion of patients who have successful pain relief after surgery. Changing implant design has historically been a target for improving outcome, but there is greater recognition that improvements can be achieved by better implantation methods, avoiding complications, and improving perioperative care for patients, such as enhanced recovery programmes. New technologies are likely to advance future knee replacement care further, but their introduction must be regulated and monitored with greater rigour to ensure patient safety.
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http://dx.doi.org/10.1016/S0140-6736(18)32344-4DOI Listing
November 2018

Central Sensitization in Knee Osteoarthritis: Relating Presurgical Brainstem Neuroimaging and PainDETECT-Based Patient Stratification to Arthroplasty Outcome.

Arthritis Rheumatol 2019 04 6;71(4):550-560. Epub 2019 Mar 6.

University of Oxford, Oxford, UK.

Objective: The neural mechanisms of pain in knee osteoarthritis (OA) are not fully understood, and some patients have neuropathic-like pain associated with central sensitization. To address this, we undertook the present study in order to identify central sensitization using neuroimaging and PainDETECT and to relate it to postarthroplasty outcome.

Methods: Patients awaiting arthroplasty underwent quantitative sensory testing, psychological assessment, and functional magnetic resonance imaging (fMRI). Neuroimaging (fMRI) was conducted during punctate stimulation (n = 24) and cold stimulation (n = 20) to the affected knee. The postoperative outcome was measured using the Oxford Knee Score, patient-reported moderate-to-severe long-term pain postarthroplasty, and a range of pain-related questionnaires.

Results: Patients with neuropathic-like pain presurgery (identified using PainDETECT; n = 14) reported significantly higher pain in response to punctate stimuli and cold stimuli near the affected joint (P < 0.05). Neural activity in these patients, compared to those without neuropathic-like pain, was significantly lower in the rostral anterior cingulate cortex (P < 0.05) and higher in the rostral ventromedial medulla (RVM) during punctate stimulation (P < 0.05), with significant functional connectivity between these two areas (r = 0.49, P = 0.018). Preoperative neuropathic-like pain and higher neural activity in the RVM were associated with moderate-to-severe long-term pain after arthroplasty (P = 0.0356).

Conclusion: The psychophysical and neuroimaging data suggest that a subset of OA patients have centrally mediated pain sensitization. This was likely due to supraspinally mediated reductions in inhibition and increases in facilitation of nociceptive signaling, and was associated with a worse outcome following arthroplasty. The neurobiologic confirmation of central sensitization in patients with features of neuropathic pain, identified using PainDETECT, provides further support for the investigation of such bedside measures for patient stratification, to better predict postsurgical outcomes.
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http://dx.doi.org/10.1002/art.40749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430421PMC
April 2019

Temporal trends and regional variation in the rate of arthroscopic knee surgery in England: analysis of over 1.7 million procedures between 1997 and 2017. Has practice changed in response to new evidence?

Br J Sports Med 2019 Dec 2;53(24):1533-1538. Epub 2018 Oct 2.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objectives: We investigated trends and regional variation in the rate of arthroscopic knee surgery performed in England from 1997-1998 to 2016-2017.

Design: Cross-sectional study of the national hospital episode statistics (HES) for England.

Methods: All hospital episodes for patients undergoing a knee arthroscopy between 1 April 1997 and 31 March 2017 were extracted from HES by procedure code. Age and sex-standardised rates of surgery were calculated using Office for National Statistic population data as the denominator. Trends in the rate of surgery were analysed by procedure both nationally and by Clinical Commissioning Group (CCG).

Results: A total of 1 088 872 arthroscopic partial meniscectomies (APMs), 326 600 diagnostic arthroscopies, 308 618 knee washouts and 252 885 chondroplasties were identified (1 759 467 hospital admissions; 1 447 142 patients). The rate of APM increased from a low of 51/100 000 population (95% CI 51 to 52) in 1997-1998 to a peak at 149/100 000 (95% CI 148 to 150) in 2013-2014; then, after 2014-2015, rates declined to 120/100 000 (95% CI 119 to 121) in 2016-2017. Rates of arthroscopic knee washout and diagnostic arthroscopy declined steadily from 50/100 000 (95% CI 49 to 50) and 47/100 000 (95% CI 46 to 47) respectively in 1997-1998, to 4.8/100 000 (95% CI 4.6 to 5.0) and 8.1/100 000 (95% CI 7.9 to 8.3) in 2016-2017. Rates of chondroplasty have increased from a low of 3.2/100 000 (95% CI 3.0 to 3.3) in 1997-1998 to 51/100 000 (95% CI 50.6 to 51.7) in 2016-2017. Substantial regional and age-group variation in practice was detected. In 2016-2017, between 11% (22/207) and 16% (34/207) of CCGs performed at least double the national average rate of each procedure.

Conclusions: Over the last 20 years, and likely in response to new evidence, rates of arthroscopic knee washout and diagnostic arthroscopy have declined by up to 90%. APM rates increased about 130% overall but have declined recently. Rates of chondroplasty increased about 15-fold. There is significant variation in practice, but the appropriate population intervention rate for these procedures remains unknown.
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http://dx.doi.org/10.1136/bjsports-2018-099414DOI Listing
December 2019

Adverse outcomes after arthroscopic partial meniscectomy: a study of 700 000 procedures in the national Hospital Episode Statistics database for England.

Lancet 2018 11 24;392(10160):2194-2202. Epub 2018 Sep 24.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: Arthroscopic partial meniscectomy is one of the most common orthopaedic procedures worldwide. Clinical trial evidence published in the past 6 years, however, has raised questions about the effectiveness of the procedure in some patient groups. In view of concerns about potential overuse, we aimed to establish the true risk of serious complications after arthroscopic partial meniscectomy.

Methods: We analysed national Hospital Episode Statistics data for all arthroscopic partial meniscectomies done in England between April 1, 1997, and March 31, 2017. Simultaneous or staged (within 6 months) bilateral cases were excluded. We identified complications occurring in the 90 days after the index procedure. The primary outcome was the occurrence of at least one serious complication within 90 days, which was defined as either myocardial infarction, stroke, pulmonary embolism, infection requiring surgery, fasciotomy, neurovascular injury, or death. Logistic regression modelling was used to identify factors associated with complications and, when possible, risk was compared with general population data.

Findings: During the study period 1 088 782 arthroscopic partial meniscectomies were done, 699 965 of which were eligible for analysis. Within 90 days, serious complications occurred in 2218 (0·317% [95% CI 0·304-0·330]) cases, including 546 pulmonary embolisms (0·078% [95% CI 0·072-0·085]) and 944 infections necessitating further surgery (0·135% [95% CI 0·126-0·144]). Increasing age (adjusted odds ratio [OR] 1·247 per decade [95% CI 1·208-1·288) and modified Charlson comorbidity index (adjusted OR 1·860 per 10 units [95% CI 1·708-2·042]) were associated with an increased risk of serious complications. Female sex was associated with a reduced risk of serious complications (adjusted OR 0·640 [95% CI 0·580-0·705). The risk of mortality fell over time (adjusted OR 0·965 per year [95% CI 0·937-0·994]). Mortality, myocardial infarction, and stroke occurred less frequently in the study cohort than in the general population. The risks of infection and pulmonary embolism did not change during the study, and were significantly higher in the study cohort than in the general population. For every 1390 (95% CI 1272-1532) fewer knee arthroscopies done, one pulmonary embolism could be prevented. For every 749 (95% CI 704-801) fewer procedures done, one native knee joint infection could be prevented.

Interpretation: Overall, the risk associated with undergoing arthroscopic partial meniscectomy was low. However, some rare but serious complications (including pulmonary embolism and infection) are associated with the procedure, and the risks have not fallen with time. In view of uncertainty about the effectiveness of arthroscopic partial meniscectomy, an appreciation of relative risks is crucial for patients and clinicians. Our data provide a basis for decision making and consent.

Funding: UK National Institute for Health Research.
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http://dx.doi.org/10.1016/S0140-6736(18)31771-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238020PMC
November 2018