SUpervised exercise- therapy and Patient Education Rehabilitation

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

SUpervised exercise- therapy and Patient

Education Rehabilitation (SUPER)

versus minimal intervention for young

adults at risk of knee osteoarthritis after

ACL reconstruction: SUPER- Knee

randomised controlled trial protocol

Adam G Culvenor ,

1,2

Thomas J West,

1,2

Andrea M Bruder,

1,2

Mark J Scholes,

1,2

Christian J Barton,

1,2

Ewa M Roos ,

Edwin Oei,

Steven M McPhail,

5,6

Richard B Souza,

Jusuk Lee,

Brooke E Patterson ,

1,2

Michael A Girdwood,

1,2

Jamon L Couch,

1,2

Kay M Crossley

1,2

To cite: CulvenorAG, WestTJ,

BruderAM, etal. SUpervised

exercise- therapy and Patient

Education Rehabilitation

(SUPER) versus minimal

intervention for young adults at

risk of knee osteoarthritis after

ACL reconstruction: SUPER-

Knee randomised controlled

trial protocol. BMJ Open

2023;13:e068279. doi:10.1136/

bmjopen-2022-068279

► Prepublication history and

additional supplemental material

for this paper are available

online. To view these les,

please visit the journal online

(http://dx.doi.org/10.1136/

bmjopen-2022-068279).

AGC and TJW are joint rst

authors.

Received 13 September 2022

Accepted 20 December 2022

For numbered afliations see

end of article.

Correspondence to

Dr Adam G Culvenor;

a. culvenor@ latrobe. edu. au

Protocol

employer(s)) 2023. Re- use

permitted under CC BY- NC. No

commercial re- use. See rights

and permissions. Published by

BMJ.

ABSTRACT

Introduction Anterior cruciate ligament injury and

reconstruction (ACLR) is often associated with pain,

functional loss, poor quality of life and accelerated

knee osteoarthritis development. The effectiveness of

interventions to enhance outcomes for those at high risk

of early- onset osteoarthritis is unknown. This study will

investigate if SUpervised exercise- therapy and Patient

Education Rehabilitation (SUPER) is superior to a minimal

intervention control for improving pain, function and quality

of life in young adults with ongoing symptoms following

ACLR.

Methods and analysis The SUPER- Knee Study is a

parallel- group, assessor- blinded, randomised controlled

trial. Following baseline assessment, 184 participants

aged 18–40 years and 9–36 months post- ACLR with

ongoing symptoms will be randomly allocated to one

of two treatment groups (1:1 ratio). Ongoing symptoms

will be dened as a mean score of <80/100 from four

Knee injury and Osteoarthritis Outcome Score (KOOS

)

subscales covering pain, symptoms, function in sports

and recreational activities and knee- related quality of

life. Participants randomised to SUPER will receive a

4- month individualised, physiotherapist- supervised

strengthening and neuromuscular programme with

education. Participants randomised to minimal intervention

(ie, control group) will receive a printed best- practice

guide for completing neuromuscular and strengthening

exercises following ACLR. The primary outcome will be

change in the KOOS

from baseline to 4 months with a

secondary endpoint at 12 months. Secondary outcomes

include change in individual KOOS subscale scores,

patient- perceived improvement, health- related quality of

life, kinesiophobia, physical activity, thigh muscle strength,

knee function and knee cartilage morphology (ie, lesions,

thickness) and composition (T2 mapping) on MRI. Blinded

intention- to- treat analyses will be performed. Findings will

also inform cost- effectiveness analyses.

Ethics and dissemination This study is approved by the

La Trobe University and Alfred Hospital Ethics Committees.

Results will be presented in peer- reviewed journals and at

international conferences.

Trial registration number ACTRN12620001164987.

INTRODUCTION

Anterior cruciate ligament (ACL) rupture is

one of the most common serious knee inju-

ries in young, healthy people participating

in sports involving jumping, pivoting and

cutting activities.

Treatment success is often

judged on a timely return to sport.

Yet, 55%

do not return to competitive sport,

and half

will develop post- traumatic knee osteoar-

thritis (OA), unacceptable persistent pain,

functional loss and poor quality of life before

STRENGTHS AND LIMITATIONS OF THIS STUDY

⇒ The exercise- therapy programme was developed

and piloted with patients and clinicians, aligns with

American College of Sports Medicine recommenda-

tions and is described based on the Consensus on

Exercise Reporting Template.

⇒ Sufciently powered trial evaluating change from

baseline to 4 months (primary endpoint) and 12

months facilitating longer- term effectiveness eval-

uation of exercise- therapy and education.

⇒ This trial will evaluate both the illness (ie, symp-

toms) and disease (ie, structure) of osteoarthritis

and include cost- effectiveness analysis.

⇒ While outcome assessors are blinded to group

allocation and physiotherapists delivering the in-

tervention are blinded to the control intervention,

participant blinding was not possible due to the type

of interventions.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

the age of 40 years.

4–7

Occupational and carer responsibil-

ities in many of these young adults also create formidable

societal and economic burden.

OA can be characterised by symptoms such as pain and

functional limitations and/or structural joint changes

seen on imaging. Both symptoms and structural changes

are common within the first decade after ACL reconstruc-

tion (ACLR), yet they are often discordant.

5 8

Interna-

tional government- endorsed OA initiatives recommend

evaluating symptoms and structure in OA clinical trials to

address the heterogeneity of the disease.

Identifying interventions that can improve knee-

related symptoms and prevent or slow structural changes

in young adults following ACLR is an international

priority.

10 11

Exercise- therapy improves pain and function

in older populations with primary (non- traumatic) knee

OA,

but effective treatments to improve structure (ie,

disease- modifying interventions) have thus far proven

elusive.

Secondary prevention strategies for those with

early manifestations (or at high risk) of OA, such as

following ACLR, offer potential to alter the OA trajec-

tory.

14 15

Targeted exercise- therapy might slow structural

worsening,

with preliminary studies reporting improved

knee cartilage composition in people at risk of OA (post-

meniscectomy)

and with non- traumatic early OA over 4

and 12 months, respectively.

18 19

People who report inadequate recovery (ongoing symp-

toms and impaired function) 1 year after ACLR are likely

to have worsening symptoms and rapidly deteriorating

joint structure in the future.

20–22

These young adults with

inadequate recovery urgently need treatment options to

alter their OA trajectory. Our feasibility study indicated

that a full- scale randomised controlled trial (RCT) eval-

uating a physiotherapist- led, exercise- therapy and educa-

tion programme for young adults with ongoing symptoms

approximately 1 year after ACLR (ie, when no further

improvement is likely without treatment) is feasible and

likely associated with a clinically worthwhile effect for

pain, function and quality of life.

The primary aim of this RCT is to estimate the average

effect of SUpervised exercise- therapy and Patient Educa-

tion Rehabilitation (SUPER) compared with a minimal

intervention control on knee- related pain, function and

quality of life in young adults with ongoing symptoms

at high risk of early- onset knee OA 9–36 months after

ACLR. We hypothesise that the SUPER intervention will

result in greater improvements in knee- related pain,

symptoms, function and quality of life after 4 months

(primary endpoint) and 12 months (secondary endpoint)

compared with a minimal intervention control. Secondary

aims are to assess 4- month and 12- month effectiveness

of SUPER on: (1) self- reported global rating of change

(GROC) and achievement of acceptable symptoms; (2)

health- related quality of life; (3) physical activity; (4)

kinesiophobia; (5) thigh muscle strength and function;

and (6) change in knee cartilage health. Intervention and

healthcare resource use will also be recorded to inform

economic evaluation.

METHODS AND ANALYSIS

Study design

This study protocol describes a pragmatic, parallel-

group assessor- blinded RCT conforming to the Standard

Protocol Items: Recommendations for Interventional

Trials statement.

Reporting of the completed RCT will

conform to the Consolidated Standards of Reporting

Trials statement for reporting RCTs

in conjunction

with the Template for Intervention Description and

Replication (TIDieR),

and the Consensus on Exercise

Reporting Template (CERT) guidelines.

The trial will

be conducted at a single university site (La Trobe Univer-

sity) in Melbourne, Australia with enrolment planned to

occur over 3 years (2021–2023) and 12- month follow- up

completed in 2024. The primary endpoint will be at 4

months (immediately following the intensive supervised

exercise- therapy phase), with additional follow- up at a

minimum of 12 months (further longer- term follow- up

dependent on funding). The study was prospectively

registered on the Australian & New Zealand Clinical Trial

Registry (ACTRN12620001164987).

Participants

One hundred and eighty- four young adults fulfilling the

eligibility criteria (table 1) will be included.

Recruitment procedure

Trial flow is outlined in figure 1. Participants will be

recruited from approximately 15 collaborating private

orthopaedic surgeons and 8 public hospital sites in

Victoria, Australia. Consistent with our pilot work,

28 29

potentially eligible participants (ie, individuals with an

ACLR from our network of collaborating private ortho-

paedic surgeons or public hospitals) will be mailed study

information inviting them to contact a member of the

research team. Additional participants will be recruited

from the general community via advertisements in local

newspapers, community magazines and newsletters (eg,

university staff bulletins, sports club newsletters), posters

in the community and social media.

Volunteers responding to the invitation letter or adver-

tisements will be screened for eligibility using a three-

stage process. First, screening questions will be asked via

telephone or email. Second, potentially suitable volun-

teers will be sent the Knee injury and OA Outcome Score

(KOOS) questionnaire electronically (or hard copy if

preferred) to confirm symptomatic eligibility. Third, base-

line MRI scans will be assessed to confirm the absence of

any pathology potentially necessitating surgery (eg, graft

rupture, symptomatic cyclops lesion). If both knees are

eligible, the most symptomatic knee will be considered as

the index knee for the trial.

Randomisation procedure, concealment of allocation and

blinding

Eligible, willing and consenting volunteers will be

randomised to the SUPER or control group after base-

line assessment, commencing as soon as possible. A

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

computer- generated randomisation schedule has been

developed a priori by an independent statistician in

random permuted blocks of 4–8 to maintain a periodical

allocation ratio of 1:1. To ensure concealed allocation,

the randomisation schedule will be stored electroni-

cally in the secure Research Electronic Data Capture

(REDCap) system and only accessible to an unblinded

researcher once baseline measures have been obtained.

Investigators conducting study assessments will be

blinded to group allocation. As the primary outcome is

self- reported, participants are considered assessors; there-

fore, participants (and thus assessors) will be blinded to

previous scores. Physiotherapists and participants cannot

be blinded to group allocation owing to the type of inter-

ventions. An independent statistician, blinded to group

allocation, will perform the primary RCT analysis. To

reduce risk of interpretation bias, blinded results from

the analyses (group A compared with group B) will be

presented to all authors, who will agree on two alternative

written interpretations before the data manager unblinds

the randomisation code.

Interventions

Supervised exercise-therapy and Patient Education Rehabilitation

Participants allocated to SUPER will participate in a

supervised exercise programme, developed based on best

available evidence for patients with ACLR and other knee

injuries including OA,

31–33

and with input from patients

and experienced physiotherapists. An overview of the

SUPER programme aligning to the CERT guidelines is

contained in online supplemental file 1 and summarised

as per TIDieR guidelines in table 2. The SUPER inter-

vention aims to increase lower- limb muscle strength,

endurance and power, functional performance and

neuromuscular control, increase understanding of knee

health, facilitate return to desired sports activity and

enhance physical activity. Registered physiotherapists

with ≥3 years of experience treating patients following

ACLR will deliver SUPER in community settings following

a 4- hour training workshop supplemented with 3 hours of

online webinars. To minimise participant travel burden,

study physiotherapists will be located at 12–14 private

physiotherapy clinics across greater Melbourne and

regional Victoria.

SUPER is divided into two phases:

Phase 1 (0–4 months). Participants will be provided with

details of the SUPER intervention verbally and via an inter-

vention handbook detailing all exercises and an exercise

logbook, and provided access to videos of all exercises.

Participants will complete their exercise programme

supervised by a physiotherapist twice per week in phase

1, with at least one additional unsupervised session at a

gym or home encouraged (table 2). Participants/physio-

therapists will also have the option of a second opinion

by a member of our clinical expert physiotherapy team

if SUPER is failing to facilitate improvement (either at 2

or 4 months post- baseline). Second opinion will provide

assessment and guidance on exercise- therapy and patient

education needs.

Phase 2 (5–12 months). The intervention provided in

phase 2 will depend on whether the following predefined

criteria are met at the 4- month follow- up assessment:

participant’s goals are met (ie, goals set with treating

physiotherapist at start of phase 1), participant satisfied

with current symptoms/function (ie, responded ‘yes’

to patient- acceptable symptom state question (see the

Outcomes section for details)) and GROC reported as at

least ‘better’.

Table 1 Eligibility criteria

Inclusion criteria Exclusion criteria

Aged 18–40 years at the time of ACLR Synthetic ACLR graft

9–36 months following ACLR Concomitant intra- articular knee fracture

Symptomatic ACLR knee: mean score of <80/100

from four Knee injury and OA Outcome Score

subscales covering pain, symptoms, function in

sports/recreation and quality of life

Planning to relocate interstate/internationally in following 12 months or

unable to commit to study assessments

Willing and able to participate in exercise- therapy

2–3 times per week for at least 4 months

Any of the following in the past 3 months: knee re- injury, surgery or

injection (either knee)

Undertaken rehabilitation in past 6 weeks (for conditions affecting either

knee)

Contraindications to MRI

Planning knee surgery in following 12 months (eg, graft rupture, cyclops

lesion (localised anterior arthrobrosis) on MRI)

Other reasons for exclusion (health condition affecting physical function,

mentally unable to participate, pregnancy, unable to understand English,

etc)

ACLR, anterior cruciate ligament reconstruction; OA, osteoarthritis.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

For participants meeting all criteria, phase 2 will

involve ongoing independent exercise- therapy sessions

(approximately 30–60 min duration, two to three times

per week at a gym or home). Participants may request

a physiotherapy booster session if they become unsure

about continuing self- management or exercise- therapy

or predefined criteria are no longer met. Booster sessions

can continue once per week and will focus on the priority

exercises and discussion of self- management strategies.

Participants not meeting all criteria at the end of phase

1 will be offered ongoing once per week supervised

exercise- therapy in phase 2. Once all criteria are met,

participants will continue unsupervised exercise- therapy

sessions at a gym or home with physiotherapy booster

sessions as required (as per above criteria). All partic-

ipants will be offered a membership to a local gym to

encourage unsupervised exercise- therapy during phase

2. An additional booster session with the treating phys-

iotherapists will occur at 8 and 11 months post- baseline.

Exercise- therapy will be tailored to each participant

to match their individual preferences, goals and clin-

ical presentation (eg, muscle strength, pain severity, and

personal, sporting, work and functional needs). The

exercise- therapy programme consists of five ‘priority’

exercises and four optional exercises (table 2 and online

supplemental file 2). The total number of exercises

prescribed (maximum number of nine) will depend on

the participant’s available time and willingness, and phys-

iotherapist clinical reasoning—but will always include the

five ‘priority’ exercises.

Each exercise has three to six levels of difficulty. Phys-

iotherapists will supervise and progress exercises based

on defined criteria guided by American College of Sports

Medicine strength training principles

and perceived

difficulty using rating of perceived exertion and minimal

pain (eg, <3/10 on Numerical Pain Scale) (details in

online supplemental file 1).

Figure 1 Flow of participants through the study. KOOS, Knee injury and Osteoarthritis Outcome Score; RCT, randomised

controlled trial; SUPER, SUpervised exercise- therapy and Patient Education Rehabilitation.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

Table 2 Overview of intervention delivery described according to the TIDieR guidelines

Brief name SUPER intervention Minimal intervention control

Why Exercise- therapy to enhance muscle strength, function

and physical activity can improve pain and quality of life in

older adults with OA

and address risk factors for post-

traumatic OA.

The booklet was produced based on information

provided to patients and thus, accurately reects usual

care.

What materials Participants receive an intervention handbook detailing all

study details, exercises and logbook, and access to videos

of all exercises.

Participants receive a ‘best- practice guide’ booklet

of possible exercises with no specic exercise

prescription frequency.

What procedures Five priority exercises targeting: (1) weight- bearing knee

extension; (2) open- chain knee extension; (3) plyometrics;

(4) balance/agility; (5) knee exion and four optional

exercises targeting: (a) trunk; (b) hip abductors; (c) hip

adductors; (d) calf–each with 3–6 levels of difculty.

Physiotherapists prescribe strength exercises (3×8–12

reps) with perceived exertion criteria (aim ≥7/10) and

progressed as per ACSM and periodisation guidelines (1-

week/month easier ~5/10 exertion). Dedicated education

sessions at week 1 and week 4, supported by slides and

booklets.

Booklet explained at randomisation. Exercise

options provided (similar to SUPER intervention),

but not prescribed. Participants expected to

exercise unsupervised. Participants may contact the

physiotherapist by phone once only to ask questions/

get clarication.

Who provided Registered physiotherapists with ≥3 years of relevant

experience, trained to deliver all components (exercise and

education).

One appointment with a registered physiotherapist

with ≥3 years of clinical experience, not involved in

delivering SUPER intervention, to explain booklet

elements.

How Delivered supervised in groups and individually (supported

by unsupervised sessions) in phase 1, progressing to

completely unsupervised in phase 2.

Delivered unsupervised.

Where Supervised sessions at private physiotherapy clinics and

unsupervised sessions at gym/home.

Booklet explained at La Trobe University, Melbourne.

Gym and home exercise options provided.

When and how much Phase 1 (0–4 months):

Frequency and duration

Supervised sessions (30–60 min) 2 times/week

Unsupervised sessions (30–60 min) 1–2 times/week

Number of sessions:

32 supervised+16 unsupervised

Phase 2 (5–12 months):

Frequency and duration

Progress to unsupervised sessions 2–3 times weekly

(dependent on meeting predened criteria*).

Two supervised (booster) sessions at 8 and 11 months

post- baseline.

Number of sessions:

2 supervised+108 unsupervised

Unsupervised exercise- therapy (self- prescribed

frequency) after one face- to- face appointment.

Tailoring Tailored selection and progression of lower- limb muscle

strength, power and neuromuscular control exercises and

education based on participant preferences, goals and

clinical presentation.

Standardised exercise examples and education.

Modications Modications will be reported. If state and/or institution COVID- 19 pandemic restrictions prevent face- to- face

follow- up assessments, participants will be encouraged to continue assigned treatment until face- to- face

assessments can be conducted. If restrictions prevent supervised rehabilitation, telerehabilitation options will be

offered wherever possible.

How well (planned) Treating physiotherapists receive prior training in how to

deliver and supervise the programme. Fidelity assessed

by auditing. Participant adherence to supervised and

unsupervised sessions assessed through logbooks,

clinic attendance sheets and online (fortnightly/monthly)

questionnaire.

How well (actual) This will be reported in the primary paper.

*Predened criteria for ceasing supervised sessions in phase 2=participant’s goals are met, participant satised with current symptoms/function and

global rating of change reported as at least ’better’.

ACSM, American College of Sports Medicine; OA, osteoarthritis; SUPER, SUpervised exercise- therapy and Patient Education Rehabilitation; TIDieR,

Template for Intervention Description and Replication.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

Patient education was co- designed with experienced

physiotherapists and pilot study participants

and aims to

support the exercise- therapy programme and build moti-

vation and capability to sustain the exercises during and

after the initial 4- month supervised phase (table 2). Indi-

vidualised health education regarding expectations and

goals, exercise principles, improving adherence, pain/

fear management, long- term outcomes, weight control,

and appropriate physical, occupational and sporting

activity promotion will be delivered during the physio-

therapy treatment sessions. Two dedicated education

sessions of 45–60 min duration will be delivered during

phase 1 (week 1 and week 4). Participants will be coun-

selled regarding physical activity levels with a targeted

training programme adhering to Australian Physical

Activity Guidelines and given an activity monitor (Garmin

vívofit 4 activity tracker) if they do not have access to one

to support measurement and attainment of physical

activity goals.

Minimal intervention control

Reflecting current standard care, the minimal interven-

tion control group will receive a ‘best- practice guide’

booklet and one face- to- face appointment with a regis-

tered physiotherapist with ≥3 years of clinical experience

(not involved in treating participants in the SUPER inter-

vention) to explain booklet elements and answer ques-

tions about its contents. The booklet outlines similar

exercises and patient education as in the SUPER inter-

vention (online supplemental file 3). However, exercise

is expected to be performed unsupervised (table 2).

Participants may also contact the treating physiother-

apist by phone on one occasion to ask questions or get

further clarification but will not be provided with infor-

mation extending the scope of the booklet. The booklet

was produced based on the information provided by 10

high- volume orthopaedic surgeons in Melbourne to their

patients post- ACLR. Participants will be encouraged at the

4- month assessment to continue following the booklet up

until the 12- month assessment.

Irrespective of group allocation, participants will be

asked to refrain from other musculoskeletal therapies

(eg, chiropractic care, osteopathy, myotherapy, intra-

articular injections) for their knee pain during the trial.

Participants will be allowed to continue care for other

unrelated pre- existing conditions.

Data collection procedure

Data will be collected at baseline and 2, 4 and 12 months

after randomisation, with 4 months the a priori primary

endpoint as this coincides with the completion of the

supervised exercise- therapy intervention in phase 1.

Where possible, data will be collected and managed

using a secure web- based software platform (REDCap)

hosted at La Trobe University,

which has equivalent

measurement properties to paper- based completion.

This strategy was used in our pilot study following ACLR,

with demonstrated feasibility.

Paper versions will also be

available if preferred by participants.

Outcomes

Baseline characteristics

Participant characteristics including height, body mass,

waist girth, leg length, knee injury and rehabilitation

details, socioeconomic details (eg, education level,

employment status), family history of OA, sporting

history and health literacy (Rapid Estimate of Adult

Literacy in Medicine

) will be collected. Surgical details

will be recorded from surgical files including date, graft

type and concomitant injuries/procedures. We will also

record knee- related objective measures (table 3).

Primary outcome

The primary outcome is the change in KOOS

score from

baseline to 4- month follow- up. KOOS

is the mean score

for the self- reported KOOS subscales pain, symptoms,

function in sports and recreational activities and quality of

life, which has been used in RCTs following ACL injury.

The KOOS

and all KOOS subscale scores range from 0

(worst) to 100 (best). The KOOS is a valid and reliable

knee- specific questionnaire for assessing patient- reported

outcomes in various knee injury populations (eg, from

knee injury to OA) and is widely used globally.

39 40

Secondary outcomes

KOOS subscales

To allow for clinical in- depth interpretation, scores for

the five KOOS subscales will be reported individually (ie,

pain, symptoms, function in sports and recreational activ-

ities, activities of daily living and quality of life).

Physical performance

Peak isometric knee extensor and flexor muscle strength

and rate of force development will be assessed in sitting

using reliable and valid methods at 60° of knee flexion

on isokinetic equipment (Biodex Medical Systems, New

York, USA).

A battery of lower- limb functional tasks

commonly used following ACLR will assess functional

performance: (1) single hop for distance; (2) triple cross-

over hop for distance; (3) side- hop; (4) vertical hop and

(5) one- leg rise.

5 42 43

Such a battery produces high reli-

ability and sensitivity in populations following ACLR.

Details of physical performance tests are found in online

supplemental file 4.

Perceived global change score and patient-acceptable symptom

state

GROC will be assessed for pain and function with the

questions: ‘Overall, how has your knee pain changed

since the start of the study?’ and ‘Overall, how has your

knee function changed since the start of the study?’, and

answered on a 7- point Likert scale ranging from ‘much

worse’ to ‘much better’ and dichotomised to ‘improved’

(‘much better’, ‘better’) versus ‘not improved’ (‘a little

better’ to ‘much worse’). Satisfaction with current knee

function (ie, patient- acceptable symptom state (PASS))

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

will be assessed with the question: ‘Considering your knee

function, do you feel that your current state is satisfac-

tory? With knee function, you should take into account

all activities during your daily life, sport and recreational

activities, your level of pain and other symptoms, and also

your knee- related quality of life.’ This will be answered by

‘yes’ or ‘no’.

Participants not satisfied with current knee

function at follow- up assessments (ie, answering ‘no’

to the PASS question) will be asked a second question

relating to treatment failure: ‘Would you consider your

Table 3 Overview of data collection

Baseline 2 months 4 months 12 months

Participant characteristics

Age X

Sex X

Height, body mass, waist girth X X X

Country of birth X

Education level X

Living situation X

Smoking history X

Health literacy (REALM) X

Employment status X X X

Prior knee injury/treatment X

ACL injury, surgery and rehabilitation details X

Sport/activity participation X X X

Family history of osteoarthritis X

Medication use X

Comorbidities X

Flexion/extension range of motion X X X

Joint line tenderness (medial and lateral) X X X

Crepitus X X X

Effusion (sweep test) X X X

Stability (Lachman’s, pivot shift) X

Patient- reported outcomes

Knee injury Osteoarthritis Outcome Score X X X X

EQ- 5D- 5L X X X X

Tegner Activity Scale X X X X

Tampa Scale of Kinesiophobia X X X

Global rating of change X X X

Patient- acceptable symptom state X X X X

Health and Labour Questionnaire X X X

Work Limitations Questionnaire X X X

ACL- Quality of Life Questionnaire X X X

Knee pain (current and worst in last week) X X X X

Physical performance tests

Hop performance (four tests) X X X

One- leg rise X X X

Isometric thigh muscle strength X X X

Lower- limb loading X X X

MRI outcomes X X X

Average daily steps X X X

All participants will receive either a fortnightly (during phase 1) or monthly (during phase 2) online questionnaire via the secure online platform

(REDCap) (or hard copy mailed, or phone call depending on participant preference) to assess sports activity, adherence to exercise therapy and any

adverse events/other treatment.

ACL, anterior cruciate ligament; REALM, Rapid Estimate of Adult Literacy in Medicine.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

current state as being so unsatisfactory that you think the

treatment has failed?’ This will also be answered by ‘yes’

or ‘no’.

Knee joint structure

Unilateral knee MRIs will be obtained in supine with

the lower- limb in neutral alignment using a 3T scanner

(Signa Pioneer, General Electric Healthcare, Milwaukee,

USA) and 18- channel knee coil. Sequences acquired will

include proton density- weighted fat- suppressed fast spin-

echo sequences in the sagittal, coronal and axial planes,

a T2 mapping multi- echo spin- echo sagittal sequence and

a sagittal fast spoiled gradient echo sequence (figure 2

and online supplemental file 5). Changes in carti-

lage collagen content and orientation in extracellular

matrices reflecting degeneration will be defined by quan-

titative changes in T2 relaxation times

from baseline

to 4- month and 12- month follow- up assessments. Knee

cartilage thickness changes over 4 and 12 months will

also be assessed.

Post- processing software incorporating

semiautomated registration and manual segmentation

in 3D will be used for both T2 relaxation time and carti-

lage thickness. Knee OA features (eg, cartilage defects,

meniscal tears, bone marrow lesions, osteophytes) will

be scored with established scoring systems

48 49

at baseline

and 12- month follow- up by a trained reader blinded to

clinical outcomes. Individual OA feature worsening will

be defined as increase in the size or depth of lesions as

previously established.

Bone shape at the knee will also

be assessed using edge- detection semiautomated segmen-

tation with 3D triangulated meshes of bone rigidly

registered on a reference template to extract the most

important modes of variation of bone shape.

Other outcomes

Fear of movement

Knee- related fear of movement will be assessed with the

Tampa Scale for Kinesiophobia.

This scale has estab-

lished reliability and validity in musculoskeletal pain

populations.

53 54

Physical activity

The Tegner Activity Scale will assess self- reported activity

level. It is a valid and reliable numerical scale from 0 (sick

leave because of knee problems) to 10 (competitive knee-

demanding sports at an elite level), with each value indi-

cating the ability to perform certain activities.

Objective

physical activity will be captured using a Garmin vívofit 4

activity tracker (Garmin International, Kansas, USA) or

participant’s own device, if appropriate.

Quality of life

We will assess knee- related quality of life, with the ACL-

Quality of Life Questionnaire,

and health- related quality

of life with the EQ- 5D- 5L.

These measures are reliable

and valid for knee pain populations.

58 59

Lower-limb loading

Lower- limb loading will be assessed using ground reaction

force data during unilateral and bilateral weight- bearing

tasks (squat, hop and drop- jump) using force plates and

ForceDecks software (Vald Performance, UK).

Knee pain

Current and worst knee pain (and how much partici-

pants are bothered by pain) in the previous week will be

assessed on a 100 mm Visual Analogue Scale (0=no pain/

bother, 100=worst pain/bother imaginable).

Treatment-related outcomes

Adherence, exercise level/intensity and other treatments received

during the trial

Adherence with the supervised exercise- therapy sessions

(ie, number of sessions attended out of 32 possible phase

1 sessions) and intensity/progression of the exercises will

be recorded by treating physiotherapists and participants.

Inadequate adherence is defined as participating in <22

(70%) supervised sessions. Participants in both groups

will record adherence to home exercises and any co- inter-

ventions received in a logbook and via fortnightly (phase

1) and monthly (phase 2) online questionnaires.

Adverse events

Any adverse events will be recorded fortnightly during

phase 1 and monthly during phase 2 via questionnaires.

Furthermore, open probe questioning will enquire about

possible adverse events at each of the follow- ups. Health-

care use data obtained as part of cost- effectiveness anal-

ysis at final follow- up will also be checked for potential

adverse events. An adverse event is defined as any unde-

sirable experience causing participants to seek medical

treatment. A serious adverse event is defined as any

undesirable event/illness/injury classified as having the

potential to significantly compromise clinical outcome

or results in significant disability or incapacity, and those

requiring inpatient hospital care. Adverse events will be

categorised into index knee or other sites and will be

assessed for severity by the trial management committee.

Data management

Most outcome data will be collected and managed via

REDCap web- based software (hosted at La Trobe Univer-

sity), facilitating simultaneous data entry. For paper- based

data collection, data will be entered by a single investi-

gator with a second investigator conducting random

checks of a subset of manually entered documents

Figure 2 MRI protocol. (A) Sagittal fast spoiled gradient

echo sequence; (B) sagittal, coronal and axial proton density-

weighted fat- suppressed spin- echo sequence; and (C)

sagittal multi- echo spin- echo sequence.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

to ensure accuracy. For data analysis, personal data,

including participant names, contact details, date of birth

and MRI scans, will be stored on the La Trobe University

server Research Drive Storage, separately from deidenti-

fied (numbered) data. All subsequent study data will be

identified by participant number only.

Due to the minimal known risks associated with the

interventions being evaluated, this study will not have a

formal data monitoring committee and does not require

an interim analysis. Any unexpected serious adverse events

or outcomes will be discussed by the trial management

committee (identical to the authors of this protocol).

Sample size calculation

This trial has been powered to detect a clinically signifi-

cant between- group difference for the primary outcome

of KOOS

. The overall effect size for exercise therapy on

self- reported pain and disability is moderate (0.50).

With this effect size, to achieve 85% power at a two- sided

0.05 significance level on the KOOS

, 146 participants are

required. To account for a 20% drop- out, we will recruit

184 participants. This sample size will be sufficient to

detect a minimal important change (MIC) in KOOS

9 points in patients following ACLR (with SD of 15).

38 60

Stopping rule

If the intended sample size is not reached at 36 months

after recruitment commencement, the inclusion of partic-

ipants will stop at 160, which will ensure a power of 80%

for the primary outcome of KOOS

, anticipating up to

20% loss to follow- up. Including a minimum of 160 partic-

ipants will also provide ≥90% power to detect a statisti-

cally significant difference (α=0.05) on the secondary

outcome of cartilage quality on MRI (change in cartilage

T2 relaxation time) between the SUPER intervention and

minimal intervention control groups (anticipated effect

size of 0.59).

Statistical analyses

Analysis will be performed according to the intention-

to- treat principle with the statistical analyst blinded to

group allocation. Descriptive statistics and generalised

linear mixed models (adjusted for baseline measure and

referral source (private vs public) as fixed effects) will

be used to examine the effect of group allocation on the

primary and secondary outcomes. For binomial secondary

outcomes (eg, cartilage defect worsening, proportion of

participants ‘improved’ on the GROC scale, proportion of

participants who had a KOOS

change exceeding the MIC

of 9 points), binomial (logistic) family will be selected. As

this is a randomised trial, we do not plan to adjust for

other potential confounders (eg, age, sex), but if notable

imbalance between groups in potential confounders

is observed, we will examine the effect of adjusting for

potential confounders (fixed effects).

While the primary

analysis approach is intention- to- treat, per- protocol anal-

ysis will also be conducted excluding those who have

inadequate adherence with the SUPER intervention to

assist with clinical interpretation of findings. Planned

exploratory subgroup analyses including repeating anal-

ysis by injury characteristics (eg, isolated vs combined

ACL injury) will be conducted given the known risk of

a combined injury (eg, concomitant meniscal/cartilage)

on OA outcomes.

Two sensitivity analyses are planned.

The first will use multiple imputation for missing data,

assuming these data are considered missing at random.

The second will exclude participants who experienced

a subsequent new acute traumatic lower- limb injury (or

surgery) severe enough to require a period of non- weight-

bearing assuming this may have influenced the outcomes

of those participants, unless the injury was sustained while

completing the trial intervention activities.

Healthcare resource use and productivity

The resources required to deliver each intervention and

treatment- related healthcare resource use including

co- interventions for knee- related symptoms (eg, medi-

cines, complementary treatments and details of hospital

presentations) will be recorded. This information will

be collected from several sources (Medicare and Phar-

maceutical Benefits Scheme databases (rebated and

out- of- pocket costs), as well as participant logbooks and

questionnaires) for the trial period. The Health and

Labour Questionnaire

and the Work Limitations Ques-

tionnaire

will also be collected for the trial period to

inform estimates of productivity losses. Methods of cost-

effectiveness analysis will be reported elsewhere.

Process evaluation

Semistructured interviews will be conducted on a subset

of participants (until data saturation is reached) following

the intervention. Interviews will explore beliefs/experi-

ences; knowledge and understanding of interventions

received including potential benefits; acceptability and

perceived effectiveness of the intervention; and reasons

for adhering (or not) to exercise- therapy and education

provided. Purposive sampling will be used to recruit inter-

view participants based on characteristics and outcomes

of trial. Interviews will be audio recorded, transcribed and

analysed using Framework Analysis.

Data will be coded

deductively according to the code structure generated by

the interview topic guide, and an inductive thematic anal-

ysis will be applied until no new themes emerge.

Patient and public involvement

Patients and clinicians are integral throughout each

stage of this project. Patients and clinicians co- designed

the intervention, research questions and study methods.

This input was gained from: (1) discussions with leading

clinicians managing ACL injuries during SUPER devel-

opment; (2) collation of orthopaedic surgeon–patient

education material to inform the control intervention;

(3) qualitative interviews with participants and treating

physiotherapists from our pilot study as part of formal

process evaluation strategies

; (4) qualitative interviews

with symptomatic patients with an ACLR as part of our

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

previous studies

; and (5) patient and clinician focus

groups providing feedback on study recruitment mate-

rial, participant handbooks and education content.

Preliminary results will be presented and discussed with

patient representatives before the results are written up

for peer- reviewed publication. Patients and clinicians will

provide input into the dissemination of study results by

assisting with the decision on what information to share

and in what format.

ETHICS AND DISSEMINATION

This study complies with the Declaration of Helsinki and

has been approved by the La Trobe University Human

Research Ethics Committee (HEC- 19447), the Alfred

Hospital Ethics Committee (HREC 537/19) and Services

Australia External Request Evaluation Committee

(RMS0879). Written informed consent will be obtained

from participants prior to enrolment (online supple-

mental file 6).

Study outcomes will be widely disseminated through

a variety of sources. Primary and key secondary objec-

tives will be submitted to a peer- reviewed journal. Other

secondary objectives will be addressed in separate publi-

cations. Authorship will be in accordance with guidelines

provided by the International Committee of Medical

Journal Editors. Our publication strategy will be comple-

mented by submission of abstracts to key national and

international conferences. Any important protocol

amendments will be reported to the approving ethics

committees, registered at ANZCTR and communicated

in the primary RCT report.

DISCUSSION

ACL injuries and subsequent reconstructions have

increased 43% in Australia over the previous 15 years,

with similar increases observed in the USA,

and greater

increases in England.

Half of all patients undergoing

ACLR will have a poor long- term outcome including

persistent symptoms, impaired quality of life and acceler-

ated structural decline.

5–7 70

This underscores an urgent

need for secondary prevention strategies to prevent

symptomatic and structural OA decline—an epidemic of

young people with old knees.

The current RCT will be the first to evaluate the symp-

tomatic and structural benefits of a physiotherapist-

supervised exercise- therapy and education intervention

for young adults at high risk of post- traumatic knee OA.

While outcome assessors are blinded to group alloca-

tion and physiotherapists delivering the intervention are

blinded to the control intervention, owing to the type

of interventions (ie, exercise therapy and education),

blinding of participants is not possible. The difference

in frequency of physiotherapy sessions between the

two groups means that the contextual effects related to

supervised physiotherapy treatment are also not able to

be isolated. We did not include a wait- list control group

as this would have reduced equipoise and increased

the risk of resentful demoralisation (if used instead

of our minimal intervention control) and consider-

ably increased the required sample size (if used as a

third comparator group). Furthermore, only patient-

reported outcomes are collected at 2- month follow- up

to minimise participant burden. We also acknowledge

that the wrist- worn activity tracker (Garmin vívofit 4)

or other commercial devices that participants wear may

under/overestimate daily step counts; however, the

differences with research- grade accelerometers appear

minimal.

This fully powered phase III trial represents

an important step towards optimising management to

achieve better outcomes and curtail the rapid trajectory

of post- traumatic knee OA following ACL injury and

reconstruction.

Author afliations

La Trobe Sport and Exercise Medicine Research Centre, School of Allied Health,

Human Services and Sport, La Trobe University, Bundoora, Victoria, Australia

Australian IOC Research Centre, La Trobe University, Bundoora, Victoria, Australia

Department of Sports Science and Clinical Biomechanics, University of Southern

Denmark, Odense, Denmark

Department of Radiology & Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam,

The Netherlands

Australian Centre for Health Services Innovation & Centre for Healthcare

Transformation, School of Public Health & Social Work, Queensland University of

Technology, Kelvin Grove, Queensland, Australia

Clinical Informatics Directorate, Metro South Health, Woolloongabba, Queensland,

Australia

Department of Physical Therapy and Rehabilitation Science, University of California

San Francisco, San Francisco, California, USA

Department of Radiology and Biomedical Imaging, University of California San

Francisco, San Francisco, California, USA

Twitter Ewa M Roos @ewa_roos and Brooke E Patterson @Knee_Howells

Acknowledgements We thank physiotherapists, Mick Hughes and Randall

Cooper, for assistance in intervention design. We thank the orthopaedic surgeons

assisting with participant recruitment: Hayden Morris, Chris Kondogiannis, Nathan

White, Mark O’Sullivan, Matthew Evans, Ashley Carr, Justin Wong, Dirk van Bavel,

Matthew Alexander, Ben Campbell, Altay Altuntas, Simon Talbot, Raphael Hau,

Luke Spencer, David Mitchell. We thank the staff at each of the public hospitals

involved in participant recruitment: Lara Kimmel & Susan Liew (Alfred Hospital),

Emily Cross & Andrew Bucknill (Royal Melbourne Hospital), Jimmy Goulis & Juliette

Gentle (Northern Hospital), Chris Cimoli, David Berlowitz & Andrew Hardidge

(Austin Hospital), Peter Choong (St Vincent’s Hospital), Leanne Roddy & Raphael

Hau (Box Hill Hospital), Libby Spiers & Phong Tran (Footscray Hospital), Peter

Schoch, Katelyn Bailey, Caitlin Knee & Richard Page (Barwon Hospital), Leonie

Lewis & David Mitchell (Ballarat Hospital). We thank the physiotherapists involved

in treating the participants at Complete Sports Care, Clifton Hill Physiotherapy, Flex

Out Physiotherapy, Lake Health Group, Melbourne Sports Physiotherapy, Mill Park

Physiotherapy, Symmetry Physiotherapy, Grand Slam Physiotherapy, Melbourne

Sports Medicine Centre, Southern Suburbs Physiotherapy Centre, Lifecare La

Trobe.

Contributors AC, KC, CB, ER, EO and SMM conceived the study and obtained

funding. AC, KC and CB designed the study protocol with input from ER, EO and

SMM. SMM provided statistical expertise and will conduct primary statistical

analysis. EO, RBS and JL provided imaging expertise and will lead imaging

analysis. AC drafted the manuscript with input from TJW, KC, CB, ER, EO, SMM,

RBS, JL, AMB, BEP, MG, JLC and MJS. All authors have read and approved the nal

manuscript.

Funding This trial is supported by the National Health and Medical Research

Council (NHMRC) of Australia (ID: 1158500). AC is a recipient of an NHMRC

Investigator Grant (GNT2008523), CB was a recipient of a Medical Research Future

Fund Translating Research Into Practice (MRFF TRIP) Fellowship (ID: 1150439).

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

Disclaimer The funders have no role in the study design and will not have any role

in its execution, data management, analysis and interpretation or on the decision to

submit the results for publication.

Competing interests CB is the owner of a business providing physiotherapy

treatment and exercise classes for some participants enrolled in this study. CB will

have no role in the decision of which clinic participants attend for study treatment.

All other authors declare no competing interests.

Patient and public involvement Patients and/or the public were involved in the

design, or conduct, or reporting, or dissemination plans of this research. Refer to

the Methods section for further details.

Patient consent for publication Not required.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has

not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been

peer- reviewed. Any opinions or recommendations discussed are solely those

of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and

responsibility arising from any reliance placed on the content. Where the content

includes any translated material, BMJ does not warrant the accuracy and reliability

of the translations (including but not limited to local regulations, clinical guidelines,

terminology, drug names and drug dosages), and is not responsible for any error

and/or omissions arising from translation and adaptation or otherwise.

Open access This is an open access article distributed in accordance with the

Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which

permits others to distribute, remix, adapt, build upon this work non- commercially,

and license their derivative works on different terms, provided the original work is

properly cited, appropriate credit is given, any changes made indicated, and the use

is non- commercial. See:http://creativecommons.org/licenses/by-nc/4.0/.

ORCID iDs

Adam GCulvenor http://orcid.org/0000-0001-9491-0264

Ewa MRoos http://orcid.org/0000-0001-5425-2199

Brooke EPatterson http://orcid.org/0000-0002-6570-5429

REFERENCES

1 Grifn LY, Agel J, Albohm MJ, etal. Noncontact anterior cruciate

ligament injuries: risk factors and prevention strategies. J Am Acad

Orthop Surg 2000;8:141–50.

2 Culvenor AG, Crossley KM. Accelerated return to sport after anterior

cruciate ligament injury: a risk factor for early knee osteoarthritis? Br

J Sports Med 2016;50:260–1.

3 Ardern CL, Taylor NF, Feller JA, etal. Fifty- ve per cent return to

competitive sport following anterior cruciate ligament reconstruction

surgery: an updated systematic review and meta- analysis including

aspects of physical functioning and contextual factors. Br J Sports

Med 2014;48:1543–52.

4 Culvenor AG, Cook JL, Collins NJ, etal. Is patellofemoral joint

osteoarthritis an under- recognised outcome of anterior cruciate

ligament reconstruction? A narrative literature review. Br J Sports

Med 2013;47:66–70.

5 Culvenor AG, Lai CCH, Gabbe BJ, etal. Patellofemoral osteoarthritis

is prevalent and associated with worse symptoms and function after

hamstring tendon autograft ACL reconstruction. Br J Sports Med

2014;48:435–9.

6 Filbay SR, Culvenor AG, Ackerman IN, etal. Quality of life in anterior

cruciate ligament- decient individuals: a systematic review and

meta- analysis. Br J Sports Med 2015;49:1033–41.

7 Lohmander LS, Englund PM, Dahl LL, etal. The long- term

consequence of anterior cruciate ligament and meniscus injuries:

osteoarthritis. Am J Sports Med 2007;35:1756–69.

8 Patterson BE, Culvenor AG, Barton CJ, etal. Patient‐Reported

outcomes one to ve years after anterior cruciate ligament

reconstruction: the effect of combined injury and associations with

osteoarthritis features dened on magnetic resonance imaging.

Arthritis Care Res 2020;72:412–22.

9 Lane NE, Brandt K, Hawker G, etal. OARSI- FDA initiative: dening

the disease state of osteoarthritis. Osteoarthritis and Cartilage

2011;19:478–82.

10 Emery CA, Roos EM, Verhagen E, etal. OARSI clinical trials

recommendations: design and conduct of clinical trials for primary

prevention of osteoarthritis by joint injury prevention in sport and

recreation. Osteoarthritis Cartilage 2015;23:815–25.

11 Whittaker JL, Culvenor AG, Juhl CB, etal. OPTIKNEE 2022:

consensus recommendations to optimise knee health after

traumatic knee injury to prevent osteoarthritis. Br J Sports Med

2022;56:1393–405.

12 Juhl C, Christensen R, Roos EM, etal. Impact of exercise type and

dose on pain and disability in knee osteoarthritis: a systematic review

and meta- regression analysis of randomized controlled trials. Arthritis

Rheumatol 2014;66:622–36.

13 Roos EM, Arden NK. Strategies for the prevention of knee

osteoarthritis. Nat Rev Rheumatol 2016;12:92–101.

14 Pollard TCB, Gwilym SE, Carr AJ. The assessment of early

osteoarthritis. Journal of Bone and Joint Surgery 2008;90B:411–21.

15 Culvenor AG, Girdwood MA, Juhl CB, etal. Rehabilitation after

anterior cruciate ligament and meniscal injuries: a best- evidence

synthesis of systematic reviews for the OPTIKNEE consensus. Br J

Sports Med 2022;56:bjsports- 2022- 105495–53.

16 Culvenor AG, Ruhdorfer A, Juhl C, etal. Knee extensor strength

and risk of structural, symptomatic, and functional decline in knee

osteoarthritis: a systematic review and meta- analysis. Arthritis Care

Res 2017;69:649–58.

17 Roos EM, Dahlberg L. Positive effects of moderate exercise

on glycosaminoglycan content in knee cartilage: a four- month,

randomized, controlled trial in patients at risk of osteoarthritis.

Arthritis Rheum 2005;52:3507–14.

18 Munukka M, Waller B, Rantalainen T, etal. Efcacy of

progressive aquatic resistance training for tibiofemoral cartilage

in postmenopausal women with mild knee osteoarthritis:

a randomised controlled trial. Osteoarthritis Cartilage

2016;24:1708–17.

19 Koli J, MULTANEN J, KUJALA UM, etal. Effects of exercise on

Patellar cartilage in women with mild knee osteoarthritis. Med Sci

Sports Exerc 2015;47:1767–74.

20 , Spindler KP, Huston LJ, etal, MOON Knee Group. Ten- Year

outcomes and risk factors after anterior cruciate ligament

reconstruction: a moon longitudinal prospective cohort study. Am J

Sports Med 2018;46:815–25.

21 Patterson B, Culvenor AG, Barton CJ, etal. Poor functional

performance 1 year after ACL reconstruction increases the risk of

early osteoarthritis progression. Br J Sports Med 2020;54:546–55.

22 Wang Y, Teichtahl AJ, Abram F, etal. Knee pain as a predictor of

structural progression over 4 years: data from the osteoarthritis

initiative, a prospective cohort study. Arthritis Res Ther

2018;20:250.

23 Patterson BE, Barton CJ, Culvenor AG, etal. Exercise- therapy

and education for individuals one year after anterior cruciate

ligament reconstruction: a pilot randomised controlled trial. BMC

Musculoskelet Disord 2021;22:64.

24 Chan A- W, Tetzlaff JM, Gotzsche PC, etal. Spirit 2013 explanation

and elaboration: guidance for protocols of clinical trials. BMJ

2013;346:e7586.

25 Moher D, Hopewell S, Schulz KF, etal. Consort 2010 explanation

and elaboration: updated guidelines for reporting parallel group

randomised trials. BMJ 2010;340:c869.

26 Hoffmann TC, Glasziou PP, Boutron I, etal. Better reporting of

interventions: template for intervention description and replication

(TIDieR) checklist and guide. BMJ 2014;348:g1687.

27 Slade SC, Dionne CE, Underwood M, etal. Consensus on exercise

reporting template (CERT): explanation and elaboration statement. Br

J Sports Med 2016;50:1428–37.

28 Culvenor AG, Collins NJ, Guermazi A, etal. Early knee osteoarthritis

is evident one year following anterior cruciate ligament

reconstruction: a magnetic resonance imaging evaluation. Arthritis

Rheumatol 2015;67:946–55.

29 Culvenor AG, Collins NJ, Guermazi A, etal. Early patellofemoral

osteoarthritis features one year after anterior cruciate ligament

reconstruction: symptoms and quality of life at three years. Arthritis

Care Res 2016;68:784–92.

30 Järvinen TLN, Sihvonen R, Bhandari M, etal. Blinded interpretation

of study results can feasibly and effectively diminish interpretation

bias. J Clin Epidemiol 2014;67:769–72.

31 Andrade R, Pereira R, van Cingel R, etal. How should clinicians

rehabilitate patients after ACL reconstruction? A systematic review of

clinical practice guidelines (CpGs) with a focus on quality appraisal

(agree II). Br J Sports Med 2020;54:512–9.

32 Skou ST, Roos EM. Good Life with osteoArthritis in Denmark

(GLA:D™): evidence- based education and supervised neuromuscular

exercise delivered by certied physiotherapists nationwide. BMC

Musculoskelet Disord 2017;18:72.

33 Skou ST, Thorlund JB. A 12- week supervised exercise therapy

program for young adults with a meniscal tear: program development

and feasibility study. J Bodyw Mov Ther 2018;22:786–91.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from

CulvenorAG, etal. BMJ Open 2023;13:e068279. doi:10.1136/bmjopen-2022-068279

Open access

34 American College of Sports Medicine. American College of sports

medicine position stand. progression models in resistance training

for healthy adults. Med Sci Sports Exerc 2009;41:687–708.

35 Harris PA, Taylor R, Minor BL, etal. The REDCap Consortium:

building an international community of software platform partners. J

Biomed Inform 2019;95:103208.

36 Gudbergsen H, Bartels EM, Krusager P, etal. Test- Retest of

computerized health status questionnaires frequently used in the

monitoring of knee osteoarthritis: a randomized crossover trial. BMC

Musculoskelet Disord 2011;12:190.

37 Davis TC, Crouch MA, Long SW, etal. Rapid assessment of literacy

levels of adult primary care patients. Fam Med 1991;23:433–5.

38 Frobell RB, Roos EM, Roos HP, etal. A randomized trial of

treatment for acute anterior cruciate ligament tears. N Engl J Med

2010;363:331–42.

39 Roos EM, Roos HP, Lohmander LS, etal. Knee Injury and

Osteoarthritis Outcome Score (KOOS)--development of a self-

administered outcome measure. J Orthop Sports Phys Ther

1998;28:88–96.

40 Collins NJ, Prinsen CAC, Christensen R, etal. Knee injury and

osteoarthritis outcome score (KOOS): systematic review and

meta- analysis of measurement properties. Osteoarthritis Cartilage

2016;24:1317–29.

41 Drouin JM, Valovich- mcLeod TC, Shultz SJ, etal. Reliability

and validity of the Biodex system 3 pro isokinetic dynamometer

velocity, torque and position measurements. Eur J Appl Physiol

2004;91:22–9.

42 Culvenor AG, Collins NJ, Vicenzino B, etal. Predictors and effects of

patellofemoral pain following hamstring- tendon ACL reconstruction.

J Sci Med Sport 2016;19:518–23.

43 Patterson BE, Crossley KM, Perraton LG, etal. Limb symmetry

index on a functional test battery improves between one and ve

years after anterior cruciate ligament reconstruction, primarily

due to worsening contralateral limb function. Phys Ther Sport

2020;44:67–74.

44 Gustavsson A, Neeter C, Thomeé P, etal. A test battery for

evaluating hop performance in patients with an ACL injury and

patients who have undergone ACL reconstruction. Knee Surg Sports

Traumatol Arthrosc 2006;14:778–88.

45 Ingelsrud LH, Granan L- P, Terwee CB, etal. Proportion of patients

reporting acceptable symptoms or treatment failure and their

associated KOOS values at 6 to 24 months after anterior cruciate

ligament reconstruction. Am J Sports Med 2015;43:1902–7.

46 Oei EHG, van Tiel J, Robinson WH. Quantitative radiologic imaging

techniques for articular cartilage composition: toward early

diagnosis and development of disease- modifying therapeutics for

osteoarthritis. Arthritis Care Res 2014;66:1129–41.

47 Culvenor AG, Eckstein F, Wirth W, etal. Loss of patellofemoral

cartilage thickness over 5 years following ACL injury depends on the

initial treatment strategy: results from the KANON trial. Br J Sports

Med 2019;53:1168–73.

48 Hunter DJ, Guermazi A, Lo GH, etal. Evolution of semi- quantitative

whole joint assessment of knee oa: MOAKS (MRI osteoarthritis knee

score). Osteoarthritis Cartilage 2011;19:990–1002.

49 Roemer FW, Frobell R, Lohmander LS, etal. Anterior cruciate

ligament osteoarthritis score (ACLOAS): longitudinal MRI- based

whole joint assessment of anterior cruciate ligament injury.

Osteoarthritis Cartilage 2014;22:668–82.

50 Runhaar J, Schiphof D, van Meer B, etal. How to dene subregional

osteoarthritis progression using semi- quantitative MRI osteoarthritis

knee score (MOAKS). Osteoarthritis and Cartilage 2014;22:1533–6.

51 Liao Tzu‐Chieh, Jergas H, Tibrewala R, etal. Longitudinal analysis

of the contribution of 3D patella and trochlear bone shape on

patellofemoral joint osteoarthritic features. Journal of Orthopaedic

Research 2021;39:506–15.

52 Woby SR, Roach NK, Urmston M, etal. Psychometric properties

of the TSK- 11: a shortened version of the Tampa scale for

Kinesiophobia. Pain 2005;117:137–44.

53 French DJ, France CR, Vigneau F, etal. Fear of movement/(re)

injury in chronic pain: A psychometric assessment of the original

English version of the Tampa scale for kinesiophobia (TSK). Pain

2007;127:42–51.

54 Roelofs J, Goubert L, Peters ML, etal. The Tampa scale for

Kinesiophobia: further examination of psychometric properties in

patients with chronic low back pain and bromyalgia. European

Journal of Pain 2004;8:495–502.

55 Briggs KK, Lysholm J, Tegner Y, etal. The reliability, validity, and

responsiveness of the Lysholm score and Tegner activity scale for

anterior cruciate ligament injuries of the knee. Am J Sports Med

2009;37:890–7.

56 Mohtadi N. Development and validation of the quality

of life outcome measure (questionnaire) for chronic

anterior cruciate ligament deciency. Am J Sports Med

1998;26): :350–9.10.1177/03635465980260030201

57 Rabin R, de Charro F. EQ- SD: a measure of health status from the

EuroQol group. Ann Med 2001;33:337–43.

58 Fransen M, Edmonds J. Reliability and validity of the EuroQol

in patients with osteoarthritis of the knee. Rheumatology

1999;38:807–13.

59 Lafave MR, Hiemstra L, Kerslake S, etal. Validity, reliability, and

responsiveness of the anterior cruciate ligament quality of life

measure: a continuation of its overall validation. Clin J Sport Med

2017;27:57–63.

60 Roos EM, Boyle E, Frobell RB, etal. It is good to feel better, but

better to feel good: whether a patient nds treatment 'successful'

or not depends on the questions researchers ask. Br J Sports Med

2019;53:1474–8.

61 Bruder AMetal. Let’s talk about sex (and gender) after ACL injury.

A systematic review and meta- analysis of self- reported activity and

knee- specic outcomes. British Journal of Sports Medicine 2023.

62 Risberg MA, Oiestad BE, Gunderson R, etal. Changes in knee

osteoarthritis, symptoms, and function after anterior cruciate

ligament reconstruction: a 20- year prospective follow- up study. Am J

Sports Med 2016;44:1215–24.

63 Van Roijen L, Essink- bot M- L, Koopmanschap MA, etal. Labor

and health status in economic evaluation of health care: the

health and labor questionnaire. Int J Technol Assess Health Care

1996;12:405–15.

64 Lerner D, Amick BC, Rogers WH, etal. The work limitations

questionnaire. Med Care 2001;39:72–85.

65 Ritchie J, Spencer LBurgess R, ed. Qualitative data analysis for

applied policy research, in analyzing qualitative data. London:

Routledge, 1994.

66 Filbay SR, Crossley KM, Ackerman IN. Activity preferences, lifestyle

modications and re- injury fears inuence longer- term quality of life

in people with knee symptoms following anterior cruciate ligament

reconstruction: a qualitative study. J Physiother 2016;62:103–10.

67 Zbrojkiewicz D, Vertullo C, Grayson JE. Increasing rates of anterior

cruciate ligament reconstruction in young Australians, 2000- 2015.

Med J Aust 2018;208:354–8.

68 Mall NA, Chalmers PN, Moric M, etal. Incidence and trends of

anterior cruciate ligament reconstruction in the United States. Am J

Sports Med 2014;42:2363–70.

69 Abram SGF, Price AJ, Judge A, etal. 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;54:286–91.

70 Culvenor AG, Øiestad BE, Hart HF, etal. Prevalence of knee

osteoarthritis features on magnetic resonance imaging in

asymptomatic uninjured adults: a systematic review and meta-

analysis. Br J Sports Med 2019;53:1268–78.

71 Modave F, Guo Y, Bian J, etal. Mobile device accuracy for step

counting across age groups. JMIR Mhealth Uhealth 2017;5:e88.

72 Whittaker JL, Roos EM. A pragmatic approach to prevent post-

traumatic osteoarthritis after sport or exercise- related joint injury.

Best Pract Res Clin Rheumatol 2019;33:158–71.

on August 3, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2022-068279 on 18 January 2023. Downloaded from