Jared:
Today's podcast is a debate slash conversation between Christian Barton and Marius Henriksen , moderated by yours Truly, the impetus for this debate has been the publication of several thought-provoking studies on hip and mainly knee osteoarthritis in the past 12 months, which have prompted even the staunchest advocate of exercise to question its clinical effectiveness and position as a core treatment recommendation for osteoarthritis. The disco trial, which will serve as the foundation for today's debate, is a key study that challenges the efficacy of exercise for knee osteoarthritis. We will explore this in much greater detail in the podcast proper. One of the disco trials lead authors, Marius Henriksen , who is a clinical professor of physiotherapy at Copenhagen University and the Parker Institute at Copenhagen University Hospital joins us for today's podcast. Marius will do intellectual battle with Christian Barton, who is an associate professor at Latrobe University in Melbourne. Christian also leads GLAD Australia, which aims to improve access to exercise and education to all Australians with osteoarthritis.
Jared:
GLAD exercise and education was used in the disco trial and given Christian's association with glad. I thought a conversation between Christian and Marius on the value of exercise or lack thereof, or knee osteoarthritis, was much needed as is the norm. This trial prompted benign mudslinging on Twitter, which is fun and enjoyable to observe and chime in on occasionally, but rarely does it push the conversation forward. The aim of this podcast was to get two people from seemingly opposite sides of the conversation in the same virtual room to bash out what is the role for exercise therapy in the management of Neos osteoarthritis. Before we start the podcast, a quick note from our sponsor, klino Klino is a practice management software that's used by 65,000 practitioners worldwide. It's great for busy physios, which is why it's an endorsed partner of the Australian Physiotherapy Association and the Chartered Society of Physiotherapy.
Jared:
In the uk, you'll find everything you need to run a successful physio practice in one place, like treatment notes, digital forms, online booking tools, customizable body charts, and much more. Linco meets privacy legislation for Australia, the uk, the US and Canada. So wherever you're based, Linco will help keep you compliant. Charitable donations and giving back are a big part of Clinico. A minimum of 2% of all clinic subscriptions are donated to charity each month, which means more than 1 million Australian dollars in total has been donated since Clinico was founded. Shoulder Physio Podcast listeners can get 60 days for free. Signing up takes less time than this message. Visit clinico.com/shoulder physio. Without any further delay, I bring to you my conversation between Christian Barton and Marius Henriksen . Marius Henriksen and Christian Barton. Welcome to the show.
Christian:
Thanks for having us, Jared.
Marius:
Thank you very much.
Jared:
You're very welcome. So we've got Marius over in Copenhagen, Denmark, and we've got Christian down in Melbourne, Victoria. Two of these cities are the most livable cities in the world. So you're, you're going all right. You're putting me to shame up here in dodgy Queensland. So, respect. So fellas, before we get into the, into the show, I want you both to really briefly introduce yourselves. I'm sure listeners know who you are, but Marius, let's start with you. Who are you? What do you do, mate?
Marius:
Well, my name is Marius Henriksen and I'm a clinical professor of physical therapy here at the University of Copenhagen. And I'm based at something called the Parker Institute that is a clinical research institute at the Copenhagen University Hospital. And we have a variety of focuses, but I'm mainly focused on musculoskeletal pain, mainly osteoarthritis, pain, and,how we can manage that in a non-surgical way. So,that's,exercise, weight loss, and pharmaceuticals basically. So I conduct and design a lot of clinical trials and have my PhD student and, and,postgraduate students. That's my main,my main line of work. And I've been doing this for the last 20 years, not as a professor, but uin, in this research area.
Jared:
Yeah. Are you, are you a physio by trade MAs?
Marius:
I'm a physio by training, yes. Graduated many years ago now, but seems like yesterday.
Jared:
Cool. Are you still a young and vibrant a Christian? What about you, mate?
Christian:
Yeah, so I'm a clinician researcher, so physio background practiced and completed research together for the last 15 plus years. And most of my clinical practice and research align. So looking at persistent knee pain, so from younger people, adolescents, telereal, pain through to older populations with knee neo osteoarthritis. Clinically I really like seeing running injuries, in particular people with knee osteoarthritis wanting to continue running or get back to running. It's harder to get research funding for running related research but I like to do that clinically in my research program. I started off doing a lot of biomechanics research in a gait lab, 3D motion analysis, and then slowly transitioned through my interest in behavior change and implementation, more towards implementation science, and do a lot of qualitative research these days and, and run more knowledge translation research programs related particularly to neo osteoarthritis, but also dabble in oncology rehab and low back pain, plantar hillel pain, various upper musculoskeletal conditions, tendinopathy, et cetera.
Jared:
Awesome. Busy. Both busy. So I wanna ask you both a personal question because just to, I haven't, this is unscripted. So this is just come to me cause I want people to figure out who you guys are apart from your intellectual and professional jobs. What do you do for fun, Marius? What's your, what's your, what's your hobbies? What do you like to do?
Marius:
I love to cook and eat.
Jared:
Cook and eat
Marius:
That cook and eat. Yeah. So, so that needs to be where a delicately dosed unless you wanna have a larger version of me. And then I love to go by the ocean and, and on the ocean on my wind surfer. So yeah.
Jared:
Awesome. Christian.
Christian:
Yeah, so I'd probably have a pretty strong obsession with football, Australian rules, football for those international and even new in Queensland, Jared, the, where we actually do kick the ball and don't throw it around. So played up until a few years ago and now I've got three young kids who are all obsessed with it. So going along to watch it and also playing with them probably activity-wise. Do more running these days, although I'm flirting with the idea of making it come back to footy. But yeah, running, I've got a seven year old who's got a park run pb, so five Ks of just over 23 minutes. So you're suddenly doing, pressuring me to try and pick up my running. And I think if I go back 18 months, two years ago, he would've beaten me. And so now my, my goal at the moment, physical activity wise, just to stay fast, him for as long as I can.
Jared:
That's awesome. 5K, 23 minutes. That's seriously impressive. Yeah,
Christian:
He's fast.
Jared:
Obviously gets it from his mum, right?
Christian:
Oh, it's not me. I've got some great family of running uncles who've won race stall and things like that in some of them two mile I inherited none of them. Zero skipped,
Jared:
Skip, skip generation. Yeah, that's right. Alright, sweet. So now we've got a little bit of humanity in the show. So let's get into the, to the nitty gritty. So Marius, you've been a driving force and a and a lead author in this, this disco trial which has come out, which, which has taken the physio world by storm and caused a lot of Twitter debates and I love it. It's caused a lot of lively discussion. So thank you for doing the work. I want you to just give us a little bit of a summary of the trial, if you don't mind, and then maybe I'll get Christian to sort of butt in and he can sort of speak for glad. But maybe Marius, just give us a little bit of a, an overview of what the trial is and what we found.
Marius:
Yes, of course. Sorry, my, my office phone just rang, I just have to check it off. Yeah, well the disco trial was a trial that we had in mind for many years. Cause we started to, to think a little bit critical about the true effect of, of exercise in general, and particularly the exercise part that was promoted as part of the program. After we have, we have worked a bit with it ourselves and kinda struggled to see, to see the rationale and, and to, to to accept that this would be an effective intervention. And then we discussed how, how could we do a study that kind of overcame some of the challenges with exercise trials. Were in osteoarthritis with, with pain as an outcome. Cause we have a problem with designing a proper control group and blinding exercise.
Marius:
So go going at it scientifically, we have a problem in, in our field of physiotherapy and exercise, therapeutic exercise. And then we came up with the idea that let's, let's control it against something that is normally used as a placebo in pharmaceutical trials. And that was the saline injections. And after a bit of forth and back with the ethical committees and funding bodies we, we set off and the signed the study where we aimed to see if, if the effects of the GLAD program was, would be equivalent to that of the comparators. So the saline injections. And we did that after voting in the, in the research group. So we actually voted who, who thinks will, who, who, who will. And we asked the investigators and it panned out that it was, it was a tie. Equally many investigators voted for the GLAD program as for the, for the saline injection and as for no difference.
Marius:
And then we decided to go with the equivalent study because that's what the prevailing, well, not prevailing, but that's what the hypothesis there were. No, we we couldn't agree to, to agree. So we agreed to disagree and then we went for the, for the test and the sign of the studies that that aim at showing that they were equally good. Then we included 200 patients and randomized them to the lab program and to the saline injections. It panned out that they were equally good at relieving pain and that has caused a bit of controversies and debates also Twitter, but around the world and well here we are to that up. Good.
Jared:
There's lots to dive into. Christian, I want you to just give us a bit of an intro into Glad Mari Marius said it a few times, but what's this GLAD program that we keep hearing about?
Christian:
Yeah, I might, before I jump into glad, I'll, I guess go to the rationale of the trial and just thinking about that. And I think Marius put together and his team put together a really good protocol and would've been quite a compelling funding argument. If you look at intraarticular saline injections, which was the control, if you compare that to no intervention, the effect size is about 0.7 across a number of trials, which was very clear in the protocol they put in. And interestingly, if you compare exercise to no intervention, then you see about the same about 0.7. So these are both reasonable effect sizes compared to just leaving people by themselves. So we, I'm sure we'll touch on saline and what we do with the considerations around that later. But it, if you go back to that common principle around exercise being better than no intervention, I guess that's probably where GLAAD emanates from.
Christian:
And we know from some of the work we've done in systematic reviews more recently that if you combine exercise with quality education, that that can also improve outcomes, particularly in the short term for both pain and function. And that's what informs guidelines of why guidelines widely recommend exercise and education. Now we know that if you look at trials that try to compare different forms of exercise, they rarely find a difference between interventions of exercise. And that can be high dose resistance training versus low dose resistance training. And when I talk about dose, I'm talking more about the magnitude of loads cetera, not necessarily how much exercise people do. If you compare aerobic exercise to resistance training compared to exercise, it might focus on function. You'll rarely find a difference. So it seems that although not all exercise is equal, if you do it across a population base, that exercise seems to win against usual care or against no intervention.
Christian:
And if you look at some of the trials that looked at cost effectiveness and thinking about measurements like health related quality of life, which is probably what we need to really consider as physios, it's really clear that it's beneficial as well and, and cost effective over a couple of years in these trials. So the purpose of GLAD I guess, emanated from Denmark and we were inspired at Latrobe by what they'd managed to do in terms of, we see huge variation in what physios provide in clinical practice, some really good physios and some really good education and exercise interventions and others won't provide any exercises, A lot of passive treatment and a lot of dependent relationships developing. And so we looked at GLAD as a implementation vehicle and we played around it to see if we could try and get a tap in here in Australia and to talk about what GLAD is.
Christian:
I think people get very caught up on the type of exercise. We all have our biases as physios and one of the greatest things GLAAD did to me was actually got me to challenge my bias around what I thought was the best exercise program. I now have some much better understanding that I was probably had a lot of biases that have now been tested and proven wrong in other trials and also experience with glaad. But essentially what it does is it provides support and a framework for training physiotherapists to implement what is guideline based care. So ensuring they have some skills and also some resources to go back to their clinic and deliver an intervention that's a bit more standardized and we don't typically see that. And then it's also got a registry behind it so we can actually evaluate outcomes in the real world.
Christian:
And that's what really excites me as a researcher is we can start to look at, alright, which people will, which populations does this program benefit most and which of the populations that we probably need to not give the program to. And we'll have our biases about what we think that is and what I think what's exciting about glad, and we're starting to look at some of this in our registry in Australia because we have more than 15,000 people. There are certainly populations who the program might not benefit, but they're equally populations who the program benefits a lot. So goes back to what he's glad it's really training, support a physiotherapist, deliver a guideline based care, and then it's evaluation of that as we go along, which is quite unique and rare within physio practice. But I'm sure we can talk about the specifics of the program a bit more as well. But that's the, the principles of it.
Marius:
Lovely. Marius, do you wanna add anything there? Yeah, I mean the Christian nicely summarized some of the very good things about the GLAB program. Mainly that it's that it's a standardized framework. What I, what we've been struggling with is more the contents that that needs to be because as Christian said, from from various systematic reviews and and overview of of the evidence, it's not possible to distinguish the effects on knee osteoarthritis pain from various types of exercises. So a strength training in various doses or aerobic or so to speak. So, so our problem is that the, the promoted exercise program in the GLAD has never been tested in a randomized trial. So they state that it is evidence-based cause all exercises is supposed to be equally good, but the neuromuscular exercise program never been put into a randomized controlled trial. And that's been promoted in, in, in the program as being evidence based. That's where we think, well, not that evidence based.
Christian:
So Mary, if I ask you a question, thinking about your belief of the program, and clearly you've got criticisms of the content of the exercise program, otherwise you probably wouldn't go down the lines of this trial. I'll ask you two questions. One is, what do you consider that's likely to be inferior of that program compared to others? And two is if you compare it to no intervention, like many other exercise trials like resistance training, aerobic training, do you believe it would come out as not being superior to no intervention if that trial was done? And why didn't you do that trial? Sorry, putting three there.
Marius:
Well, well we did that, we did that trial, but we did it after the GLAD was promoted. So we did a, the neuromuscular exercise program against no intervention and it came out well along the lines with many other studies a minor, small, small effects. We did it a little bit more intensive than what is promoted in the glad. So we did it three times week for, for 12 weeks. And the glads, they decided to do two times a week for six weeks. So, so there's a difference in the dosage that might explain that. So, so, and from our clinical expertise, I mean the, the neuromuscular exercise program that is, that is being used in the GLAD program is designed originally in Sweden for very, very severely affected neo osteoarthritis patients. And then putting that into a perspective of a very heterogeneous population with where we have young people being 55 and still working on scaffolds or, or brick layers or something like that, that are strong and, and, and get fit from their work.
Marius:
It, it, it's, it's completely in my view off off the chart and, and I mean it's not, it's not relevant for them. They kinda look at me and say, you want me to do this? Yeah, no, thanks. So, so that's, that's some of the criticism. And, and then I mean all, we all agree that patient education is, is important, but but we have never really looked into the content of the patient education. So, so it might, it may be patient education per se is evidence based, but the content has never been really explored. And I forgot all your questions, but
Christian:
That's alright. Let's, let's go back to patient education. If I go a a little bit further around that, I guess, what do you feel the neuromuscular exercise program providing GLAD is missing? So go back to your bricklayer, what is it missing, what doesn't it address?
Marius:
Well the, the premise of, of the neuromuscular exercise program is that the patients somehow are moving around in a wrong way. And the physio has the, the solution that I know how, how you should move. And that is a very orthopedic and biomechanical approach. And based on studies that we did, we did biomechanical GA analysis on, on before and after our neuromuscular exercise program for 12 weeks, three times a week. So higher dose that's presumably should be as effective as anything. And we couldn't find any changes in the biomechanics at all. So so what misses another perspective on of the disease for instance, cardio cardiometabolic aspects that is not been targeted at all.
Christian:
So if, if we go back to that concept around physios, being able to identify the wrong movement pattern and correcting, I, I tend to agree with you Marus and we have interesting discussions within the international GLAD leadership around this. And we know that the program, if you focus on some movement pattern and control and try to improve that, it can be very helpful for some people. The way we teach the course in Australia and it's evolved all around the world towards this alignment, is that you don't have to move a perfect way necessarily. This is an option you have to move differently. That can be a pain modifier and can reduce pain, but ultimately what the exercises do is they improve your, your control and and your confidence to actually engage in exercise. And so some of the outcomes that we look at in our Australian registry are around that contr not just control, but thinking more so about confidence to engage and load the knee confidence to engage and load the hip and fear of damaging the joint.
Christian:
And what we see is some really big changes with that. I think one of the big tricks you missed in your trial was actually evaluating any self-efficacy outcomes and, and anything in relation to that. Because what we do know from other recent research around mediation analysis is that seems to mediate outcomes. The other thing that's a misnomer around the world thinking about GLAD is that they think most people who haven't maybe done the training and be supported at least in Australia anyway to deliver the program, is they believe that's all the focus is, but actually the focus is around greater exposure. The focus is also around resistance training to improve capacity of your knee, sorry, quadriceps, hamstrings resistance training to improve capacity around your hip resistance training to improve capacity around your trunk. And you'll notice Jared didn't say course stability there. That was a fun one to change the terminology of in Australia when we went through it.
Christian:
So there, there's lot, lots more to the program from an exercise perspective than just that neuromuscular focus and control. And I think that's often missed in translation, especially in social media debates. And there's this dichotomy that, okay, it's all just about this, but actually the program's broader than that and I think that's important. The other thing I'll pull you up on is that a bricklayer can't benefit from it. Now I have plenty of tradespeople that come through the clinic here who absolutely love the program and benefit a lot from it. And the key is the program is designed and encouraged to be individualized and clinicians are encouraged to do that. So if someone needs additional resistance training, then they should provide that. If someone needs some calf strength because that's part of their function, they need to recover, then it's a minimal intervention. So these things can be added.
Christian:
So it's not a one size fits all and this is a structured approach. And I guess if I follow that up with a question, I'd be very curious about how you monitored what was delivered in exercise intervention in your study. Because if I look at the outcomes and the best comparison I can make is COOs quality of life, your COOs quality of life changes in both the Saline group and in your GLAD group group. We're quite low, both at three months and particularly at 12 months when we make comparisons to GLAD registry. So I guess the question to you is what did you monitor in terms of that side of things with your trial? What was being provided and what was actually being progressed and how are those progressions done? Did you look at the fidelity of those types of things or did you just leave it to the physios and hope for the best?
Marius:
Well we did monitor the the progression and we had a, a pre-specified progression scheme. So, so so that's one of the main differences between the putting a program like ladder or neuromuscular exercises into a trial versus putting it out in the real world. Because I agree that, that it is individualized and probably when people come and say, well, your effect in, in the disco trial is much lower than what we see in the, in the registries, that is because in the, the people in the registries, the co interventions are so prevalent, I should say, you can get something else, you can get a bit of mobilization or laser or common extra time or I'll give you another exercise. So we took what is protocolized and described in the lab program and tested that. So, so so, so so screaming that we're underestimating the effects, well yes, we're, but we're only testing what is being protocolized and not what what the physios feel that they should give and why do they give anything else? Is that because they kind get embarrassed or and see, well this is not enough for you, you have to get something else and then, then it's not glad anymore and it becomes very dependent on, on your own. Physio equity of providing equal care for everybody is kinda ruined cause it becomes dependent on your, on your physio. Yeah,
Christian:
The majority of people, at least in Australia, I can only speak from the Australian experience, the majority of people doing GLAAD don't get a lot of additional things. So they get additional progressions and tailoring of their exercise program, but they don't necessarily got a lot of additional love treatment. So you mentioned laser therapy. Laser therapy is almost never done in Australia that I see amongst physios. They may teach some taping as part of the process, maybe very occasional manual therapy. We very much promote to not let that get in the way of exercise. And most clinicians primarily deliver the exercise. The key part is it's individualized to the person. And I guess I go back to my question and I'd be curious and listeners would be, how did you I guess, allow the physios to progress exercises appropriately? Cuz you mentioned your bricklayer before and the program can absolutely progress be progressed for that person.
Christian:
The program can be progressed for an elite athlete if you actually have a goal at the program, has some really high level exercise and I'd challenge anyone out there to do, there's le four levels of exercises. I'd challenge anyone out there to be able to do all four levels. It's pretty tricky and pretty challenging. So I just go back to the outcomes of cos quality of life and your changes, I think of around eight at three months and then back to around four or five at 12 months. They're so, so low. So it makes me question what was actually provided in that program that you had in the trial?
Marius:
Well I cannot really answer anything that we provided what was described in the program that was brought home from the, from the courses. This is the program, this is, this is how you progress this, these are the slides for, for the so, so, so
Christian:
Just to, just to touch on that Marius it sounds like you tried to control some of that. You had a very structured framework around how things would progress. So perhaps it wasn't exactly what the training was to do. I guess I have one other really important question that always baffled me. Alex, I have two important questions that always baffled me. One being, was there any invitation from someone from GLAD to collaborate on the trial? So Soren or EVA or someone else so that we could consider some of these questions that might come up later. And the second one is, I guess trying to replicate some of the outcome measures in the GLAD registry. Looking at things beyond pain, which we know we weren't gonna see a difference in pain between saline and exercise. We knew that from the other trials. But thinking about things like joint related confidence, a bit more thinking about things like self-efficacy, thinking about health related quality of life, going back to what point I made before, that's a really key outcome. So yeah, collaboration invitations or consideration around that broader outcome measures in the program?
Marius:
Well, we had a, didn't exactly invite the GLAD people into the program, but we were in contact with them asking them if we could get some elaborations on the program or if we could do this and how is it done? And then we had GLAD certified people working on, on delivering the program. But no no direct involvement from the, which is I consider a strength because then this research is independent. So, so no biases in terms of preconception. Yeah,
Christian:
I think I agree you can consider it as strength, but I think it also probably brought up some weaknesses in the end around that broader outcome measure consideration. Also, probably potentially going back to the results and the findings may be brought up some reasons of why you maybe had lower, lower changes in, in some of the outcome measures that are used. And I, I, I really am still baffled about the, the changes there. The other question, I
Marius:
Mean mean in terms of the outcome measures, we chose the the core outcome measures set by the, which are the international associations for the study of osteoarthritis. So we took the core outcomes from that, which is pain function and patient global assessment and quality of life. So yeah,
Christian:
But not
Marius:
If, if, if glad, the GLAD people could've used or added anything other outcomes that, that are considered important by the patients.
Christian:
Yeah, I'd say that's an interesting consideration. We've done some focus group re focus groups recently with neo osteoarthritis patients and what we do in GLAD and what is in the outdoorsy criteria. None of them really resonate with people with oa, but that's a whole other story that maybe we can talk about another time. But we, we don't measure things very well at all based on patient perspectives. So if you, one of the things that you made mention of is around interventions in bladders and minimal intervention. So I guess to follow up a question with you around that, you have your three month outcomes, which in theory you've got two interventions that you're comparing beyond that there wasn't really any control around co interventions. And if you look at the co interventions, there's sort of an equal number of people in the GLAD group and the saline group doing exercise, an equal number having injections and equal number, having all these varying other things. So what can we make of the 12 month outcomes if we've got such variation in co interventions?
Marius:
Well the interesting thing is that the, the effect is quite stable, small but very stable, both for the for the injections and for for the, for the glad. And one of the important aspects of GLAD is that they state that you should consider to, to continue exercise. That is an important message that people that are gonna, the glad are, are, are sent off with and in our population they were not really sticking to the exercises at least. I'm not sure I I've seen any reports from the GLAD registry about how how often people continue exercising. So at least perhaps we, we could consider that an eight week intervention is probably not sufficient to, to to make the behavior change needed for, for people to continue exercise.
Christian:
I I agree
Marius:
Irrespective or whatever. That's too short. We can look at smoking cessation or weight loss, I mean eight weeks intervention and then believing that people are capable of doing that on their own. Nah, not really.
Christian:
Yeah, I, I mostly agree with you there. I think there's, we don't have exact data on this, but there is a, a group and a cohort does continue to do this independently especially when the program's delivered well and that independence is promoted by clinicians. One of our frustrations around fidelity and, and I think it's really important to be open about this in Australia, is we have some clinicians who try to provide the program using gym equipment. For example, we've had a really wacky experience where we had to pull up a clinic who tried to set up blood plus using Pilates equipment. That was fun. So we have to monitor this fidelity. And one of the challenges when clinicians deliver it really well, we tend to find patients are able to do it independently. Which is again, interesting from your study that not many people seem to do that. I think if we looked at it properly with clinicians delivering the program, while I think we'd see a higher rate of ongoing exercise if clinicians deliver it poorly, we'd probably see rates similar to what you saw in your trial. But we need to look at this a little bit more. It's a really good point around the short intervention and whether achieve behavior change. Sorry, Jared, I keep asking questions. You might have more.
Jared:
No, you're right. Marius, did you wanna add anything there?
Marius:
No, that's fine. I think I think I, I agree on on Christian's last point. Yeah.
Jared:
So Marius, so we'll just let you sort of finish off with the with the maybe discussion and the results a little bit more. I think we can kind of infer what the results were, but the, the two long didn't read of it is that a saline injection or multiple saline injections were effectively equivalent to eight weeks of GLAD exercise. And so a really big question that comes out of this, is this the first trial in neo osteoarthritis that has used saline injections as a control group?
Marius:
It's the first trial in in, in exercise in non-pharmacological. Yeah, so we, we kinda mix the, the pharmacological and the non-pharmacological things here, and that's some of the, that's what makes the, the, the study a little bit tricky to to, to, to break down. Because that's one of the major limitations is is that the two interventions is, is so fundamentally different.
Jared:
Yeah. So let's, so let's, so let's get into that. A lot of people are talking about, you know, how do we compare saline injections to exercise, which are fundamentally different beasts when it comes to perhaps causal mechanisms un underpinning. So how did you come to sort of using saline injections for the control group? Do you think that that's an appropriate control group going forward? And what does it give us in terms of a comparison? Like what, what, what's the clinician take home when comparing exercise to saline injections?
Marius:
Well, I'm, I'm not sure that there's a, a direct clinical implication for the, for the exercise community at least cause of, of, of the, of the choice of co comparator saline injections. But at least it, it, it, we have succeeded in, in starting a debate that was kinda absent for many years about the, the true mechanisms of exercise when we talk about pain relief. And and this debate is very sound and, and with the reason radio coming out even with even more discouraging results from, from from the Keel University I think that it's very timely that we pick up this debate and and try to, to see if, if exercise actually does have an effect on knee pain or not. This is not the same and we should not exercise or not. So, so going into recommendations and, and, and, and talking about if exercise is good for you or that's, that's another discussion that we can pick up later.
Marius:
And then regarding the, the choice of, of as a comparator that was based on that, that we have a lot of rheumatologists working here and, and they use saline as comparators and say, well that is a very good comparison when we do in particular injection studies. So if wanna test the effect of corticosteroids or hyaluronic acid saline injections is is the, is the, is a good placebo. And then we were inspired by some of the work that's been doing in open label placebo, which is a, a, a field of studies where you give patients with whatever they have of disease and iner treatment. So, so sugar pill or saline shot or something and say, well this is placebo, but mind body things, things are going on. And then we, it sure we're sure that this will help you and it and it actually is quite effective. And then we said, well, we might overcome some of the attention bias in, in the studies by doing this, knowing and accepting that there are huge differences in the root of delivery of exercise and saline ejection.
Christian:
Christian, I, I think the saline injection part is fascinating. As we mentioned before, like, and again I go back to the protocol that Mar and his team put together. Like if you compare saline to nothing, it's, it's effective, it, it does reduce pain. It's a very powerful placebo. I think it's probably not inert. There probably is an active ingredient in having some extra fluid injected into the joint. And that may be why we see potential improvements with p p compared to no intervention. Why we see potential improvements, a whole range of different injections compared to no intervention. So we don't really know the mechanism of why saline achieves, what it achieves, like we dunno the mechanism why exercise achieve what, what it achieved. So what do we do with this trial in clinical practice is a really interesting question. I don't think it really changes anything.
Christian:
Because I don't think the study was set up to really ask to me as a clinician a question that was gonna change my practice. It was set up to, to test GLAD against a different intervention that was a placebo, but I dunno, that actually tells us much because we don't have saline injections available. Maybe an interesting trial next would be to try and think more carefully about a control intervention for exercise, different types of exercise to try and tease out the active ingredients. And there was a really nice one done recently looking at heavy resistance training compared to lower resistance training. That was a great trial showed there was no difference in outcomes. That's a great use of research resources. If we think about saline, I'd love to see a sham saline injection trial. So saline injection compared to, I don't know, maybe we do what we do in acupuncture trials and use toothpicks and pretend we've done it or maybe we stick the needle in but don't inject any fluid in and and compare that, that would be a really useful trial. So if I think, again, I go back to the trial, I'm not sure what clinical question and answered, I'd probably look at some of those trials instead of, of that would be my thought. And I think, think one of the questions that people ask is, would you prescribe saline? I probably would if it was available. Cause I think it's a powerful pain reduction and I think when we send people off for a Synvisc or send them off for a prp, we're probably essentially just augmenting a really powerful placebo.
Jared:
Yeah.
Marius:
I mean in our clinic the medical doctors have taken the consequence of our research and are offering seline injections. Awesome.
Christian:
That's cool.
Marius:
So, so and, and it's done completely open and patients patient love it. And that's also some of experiences we had from, from during the trial. I mean it was open label and people say some were really amazed that this, this shot really was so effective.
Christian:
Yeah, we have, we have some sports physicians here in Melbourne that will just inject whole blood. Cause you probably get the same effect as doing a injection, for example. That's great. Mari I really, that'd be great to see them spread this. Yeah.
Marius:
And, and with, with osteoarthritis in the knee, that is the disease that we don't really know. We don't really know what's going on. We don't really have anything that is really effective.
Christian:
And, and
Marius:
I think, I think it's important for the physicians and for the physios. So first do no harm. So give an intervention that is associated with the lowest amount of side effects. And saline injection is at least in what we can see, very, very few side effects attached with it. So so why not go that way? I mean, but that's not, I'm a physio, I'm not gonna interfere with what, what the, what admitted, what the physicians are gonna do. Not gonna do. But at least I I can say that in the clinic we run, it's now being offered to select patients.
Jared:
Maurice, are are you saying that you think that saline open label salt water injection should be a mainstream treatment for keen people for neo osteoarthritis?
Marius:
Yes, I really think so because it's cheap. There's no financial incentives from anyone. And you mean there's not a company producing saline or that has a patent of
Jared:
I'm gonna register one tonight? Actually,
Marius:
Yeah, I mean you could do some, some special sailing or something like that from from the South Sea and say, well this is, I mean, and then we're in then we're in the physio business again. ,
Jared:
If there's not a naturopath that hasn't, hasn't done that, then i, I would be gobsmacked because they've got all sorts of remedies. Yeah,
Marius:
I actually believe that. But I mean that's, that's not up to me to decide. The evidence is as as good as or perhaps even better than, than for many other things that have been injected into knees.
Jared:
So, so Christian mentioned before that perhaps is an actual active or physiological effect with saline injections. And I think there's been some studies on that. What, what do you think, Maurice, do you think it's inert or do you think there's, there might be an active ingredient per se within them?
Marius:
I think it's i, I really don't know. I mean until it has been proven by by some clever immunologist or or bio biomedical researcher, I will stick to the, to the, to the fact that it's not doing anything. And it's being washed out and absorbed very, very quickly. It is physiological saline, so, so, and it's only five milliliters, so I cannot really imagine it doing anything. But there are a few minor experiments talking about osmolarity and cells senescence and, and various advanced biomedical things. But one shot of five milliliters of, of, or or even four shots every other week, one every other week or four weeks. I don't think we can see any biomedical or document any biomedical, biomedical or biological effects of anything. But I'm not, I'm open for the fact that that there may be something, but until it's proven I will stick to the fact that that so far it's in there.
Christian:
Ma Mary's a question on it cuz you might have some insight. When these participants had the saline injections, did they see quick pain reductions or what was the, was it something that's happened over a number of days or weeks or did they feel immediate relief?
Marius:
Very variable. We, we don't see a relief on on the spot. It's not like you, you jump off the table and you're relief, but, but based on the data we can see that it's within the first week of, of the first shot. You, you, you, the, the effects kick in and then the, the third, the second and third and the fourth shot are, are more like a boosters. But we don't have pain recordings just like, just before and just after. Not for that study at least.
Christian:
No it'd be interesting, interesting look at, I'm going off on a tangent, but I mean we use shockwave occasionally for persistent tendinopathies and you see really quick pain reductions and I don't think it has the mechanisms that shockwave companies promote and others promote. It has some sort of central mechanism. I think probably why it reduces pain and maybe this is a similar process. I dunno, there's more cleverer people than me that maybe need to test these and, and look at it a bit more.
Jared:
So can we go off topic a little bit gentlemen and, and talk about this, this review for exercise for hip and knee OA by I think Melanie Holden, which has come out literally just yesterday. And it's okay if you haven't read it, it, it's all good. But if you have some other opinions, the role of exercise as a primary or core treatment for hip and knee osteoarthritis. So where are we at? For, for, for me, I'll put my bias. I'll put my, I'll declare my interest here. I say I think exercise is a simple low hanging fruit cost effective, minimal harm associated with it, multiple secondary benefits associated with it. It just, it makes sense as a primary intervention. So that's, that's my bias. I, I wanna hear from you two gents. We know that Marius wants to give saline injections, everyone. Christian, what do you reckon?
Christian:
I think trial shows this, well, you can reduce pain many different ways. So saline injection manual therapy, we know that has a reduction in pain in the short term. There's a whole range of things and, and exercise the same and various types of exercise. But I think, I haven't read the, the study, it was a slightly novel study looking at pulling a lot of data from different RCTs so they won't have captured all the different RCTs available. So there may be some selection bias in those willing to share data and, and various things like that. I'm not sure, my quick scan of abstract from Twitter this morning in between doing some telehealth sessions was that there was varying non exercise interventions. So I think they included some trials that would have no treatment, other trials would have different education interventions or other usual care. So when we look at the effect, I think it would be good to tease that out a bit more.
Christian:
I dunno if you've read in that level of detail, Jared, but I think going back to the point of the trials, when you compare exercise to no intervention, it seems that there's a moderate effect. And of course this, the review for my reading briefly is that it showed a lower effect than that. So it might be that there's other non-exercise interventions that compare from a pain perspective. But go, I, I declare my bias too, Jared, and it very much aligns with you, is I think there's a lot of other benefits to exercise and it's a low hanging fruit. And when I think about it, what I'm trying to achieve in my clinical practice, so glad aside I put some people into GLAAD cause I think it's a great program for them. Others I don't send to GLAAD cause I think they need a slightly different approach and I think that's important context of that clinical reasoning.
Christian:
And I'm trying to build their self-efficacy and I'm trying to reduce their fear of loading and fear of damage. And exercise to me is almost an extension of education a lot of times. So what we're actually doing with exercise, we're telling someone it's okay to move, it's okay to be active, it's okay to go for a walk, it's okay to load your knee and do a squat and do a lunge and do all these activities. And then we're taking them through the process of graded exposure to those exercises. So I think it has to be coupled, exercise has to be coupled with education to work well. And I think that's a really important part of it for me.
Marius:
Maurice? Yeah, I mean I I I I've contributed to this review, so I read several times over the last couple of years. So I I know details quite well. And one of the, the things that is important in that is that the trials that have contributed with data, so this is, this is the not a standardized systematic review where you just pick the, the data from the articles. These are individual patient data. So, so all the authors of the individual trials have been invited to provide all data and then they only got a part of that. And then why you can speculate, only speculate why some people do not wanna share the data. Is that cause they don't have something to hide? They, they do have something to hide or are there other things that are preventing them from sharing data, but at the end what the studies that they got data from are quality objectively seen when we look at the risk of bias in these studies.
Marius:
So, so I mean the estimate from this study is probably more reliable than previous estimates and then its disappointingly low. So it's, it's on average 6.5 on a, on a zero to 100 scale effect of exercise versus no attention on pain in the short term and even worse in the longer term. So that's also an important aspect. So, so the, so the, the courthouse is falling together for exercise in terms of a pain relieving mechanism. And then I would've to say that I agree with with Christian that there's so much more to exercise than pain relief and that, and then it's it's means of, of living healthy. So, so my bias is that I don't no longer believe in exercise as a pain relieving mechanism once because the, the, the evidence tells me it's not. And two, because I've not been presented with a biological pla mechanism of why his exercise causing less pain.
Marius:
I have, I have never understood that. But that's another discussion. And then I think we should, we should we should do exercises as a means to improve health and quality of life. I mean people with neo osteoarthritis are at a severely increased risk of getting cardiovascular disease. So we should do, we should target that. That's a bigger problem than the knee pain because knee pain is not dangerous but the, the cardiovascular diseases are probably more dangerous or are more dangerous. So we should target those problems and then the knee will come along.
Christian:
I'll circle all the way back. Marius, that's one of the questions I had is I guess the reasoning of not including health related quality of life or measures of physical activity in your trial. I'm not sure where, why that occurred or whether he had a conversation about it and just wanted to focus on pain. But that's something I've always been curious on.
Marius:
Well the health quality of life, we do do have the quality of life in the questionnaire. So it's part, part of it. Measuring physical activity is cumbersome and expensive. So it's also about resources in our trial. And we have looked, we have had look at physical activity before and after glad in other, in other studies showing it's not changing anything in physical activity. And we looked at that before and after weight loss, before and after knee replacement surgically, nothing really happens. So, so if you wanna improve physical activity, you have to target that specifically, not by doing neuromuscular exercises. That's my opinion at least.
Christian:
So just for the benefits of the listeners, the cos quality of life measure is more about knee confidence I think from my perspective, whereas health related quality life takes into account a lot more things around anxiety, depression, varying other health factors. So I think they're quite different measures. So I think one should be referred to as knee related quality of life, which is cos the other is health related quality of life. And I think that's an important distinguishment.
Jared:
Marius, you said, you said a moment ago that you no longer believe in exercise as a pain relieving or pain mitigating or pain reducing treatment. So if you were a clinician and someone came to you with knee osteoarthritis and they had a strong disposition or proclivity or preference to exercise, would you say, well there is a small effect for exercise, right, against no treatment. Maybe it's the same as other intervention, but there is a small effect in terms of pain relief and it's up to the patient to decide whether that small effect is clinically important to them or not. So if somebody came to you and actually said, I wanna exercise, it's your job as a clinician to say perhaps, well this is what the research says, would you yield to them and say, okay, here's an exercise program. I'm sure you would, but run, run me through your clinical reasoning around that.
Marius:
Yeah, I would, I would definitely not discourage them from exercising and, and if they want to exercise, I would, I would put them off to an exercise program that they find fun. So, so, and I said this is not, this is for your greater wellbeing, your greater health. It's we should, we should put your knee a bit to the side here. You wanna do exercise, you wanna play, go back to play tennis or whatever, then we need to, to make you into a, a condition that is, that allows that and then explaining them that knee osteoarthritis is something that is, that is there to, to stay. It's not gonna go away. We're gonna manage this. And, and you will have bad periods and good periods and we have to dose the, the exercise to fit that. But I'm not gonna, I'm not gonna tell them that I have the magical exercise here and if you do this, you're free to go and you'll we'll see you next year or, yeah, so, so so I'm gonna, I would, I would take the more general health perspective and, and as Christian said, well empower people.
Marius:
I mean perhaps exercise is more of an empowerment tool than as a, as a pain and relieving mechanism. And that's, that would be my approach. So, so I think we're on the same page. Christian.
Jared:
Christian,
Christian:
Yeah. I think going back, I don't think you can just tell someone to do exercise that's fun because that's often what gets them into trouble. So if you say you just go do something fun, they're probably playing tennis and maybe overloading and they don't have the capacity to do that. So I think we actually do need to target the impairments that might be stopping them doing the fun part of exercise. And I think it's almost like a taking your medicine, addressing those impairments. Now whether you use the program like glad or use some other form of exercise to target those impairments it's gonna depend on the person. So if they've got muscle weakness and loss of muscle power to be able to absorb loads through their quadriceps and break and, and not load their knee up too much for running or for tennis or whatever it might be, or maybe there's hip muscle weakness that we need to address, we need to really tailor it and target it.
Christian:
So I think this whole, let's just do whatever exercise is fun, I think is a bit shortsighted for people. And I think our job as physios is to tailor it and, and target it, but with the end game being exactly what Marist is saying is getting them back to doing activity that's fun. So the end game for the, the tennis player that comes to me is going back to play tennis and playing tennis a couple times a week or whatever they want to do, but along the way they may have, may need to take some exercise medicine, so to speak and address some of their impairments. And I think if we go back to the concept of there's lots of pain relieving mechanisms that may be at play for various different interventions. We can use lots of things for pain, but if we do a saline injection and someone's lacking their muscle strength and power to be able to play tennis, we're probably not gonna have a very good outcome. And I think our job as physios is to make sure that we address those impairments. And I think that's important. I speak about marist's trial every single week with my patients. Cause I think it's a really key and important message and that is that you can actually get pain relief from many different mechanisms. And so what we need to do is individualize your care and what we provide you based on what your goals are and, and set up a, set up an intervention to help you with that.
Jared:
Ma
Marius:
Yeah, I would like to add that, that managing neo osteoarthritis or any cul condition or any condition at all is not a, you either do this or this. I mean you can do pharmaceuticals and exercise and these can probably go well hand in hand. Some, in some patients, if you reduce the pain, then you can get through with your muscle strengthening exercises. Or if you reduce an acute inflammatory response or you get relief from a, from another procedure, and then you can, you can go on with your physio. So, so we shouldn't think this as you only have to do this and nothing else. I mean, the interventions are very important, but the, the body of evidence support of of the combinations are, are not there. There's too few studies on, on, on, on synergistic ways of, of looking at this
Christian:
In, in the short term, combining education and exercise. The evidence is not super clear, but it's pretty clear that that combination is probably better than doing April line. And we have some systematic reviews that we've published recently around that space. But, and the ED point is the education interventions can be a lot better as well. They're not very well defined.
Jared:
What, what do we, what do we make of exercise being superior to corticosteroid injections into the knee for knee osteoarthritis or, or physical therapy, which included exercise. What do we make of that study, which was published a a few years ago in the New England Journal of Medicine? Anyone got any?
Marius:
Well, I have to, yeah, that was not only just exercise. That was exercise and then, and then they, they were allowed to do anything else that the physio find found relevant. So yeah, so it's more like a physiotherapy toolbox versus the the injection thing that came out. But, but yes, that's, that's kind of, there are points in the other direction than, than our studies and latest other studies. I mean, I also showed that combination of, of a steroid injection followed by exercise versus saline injections follow exercise some years back. And there were no difference between the placebo and saline and, and steroids. So that kind of kicked off the debate about steroid injections. And then now physiotherapy is superior to steroid injections. And now saline is equivalent to ex, I mean, everything is a mess and probably just a sign that, that it's all polluted by contextual factors and, and, and and cognitive bias. And, and, and, and also because we, we use pain as an outcome and that is subjective and really, really affected by so many things that are outta our control.
Jared:
Christian, any wise words?
Marius:
We're, we're back to square one. We don't know what to do. Sorry.
Christian:
I I I I agree with mar in that pain is, yeah, I mean it's a, it's embarrassed didn't use these words, but it's a very simplistic way of looking at things. And I think it's, from my perspective, it's a bit shortsighted and we need to think about things a little bit more holistically and about the person's general health and wellbeing, health related quality, life, physical activity, participation. There's a whole range of things we need to consider around that. And I think we need to target our interventions towards many things and testing that sort of thing in a clinical trial is really challenging. But we have to go to the real world. And as clinicians, our responsibility is to do similar to what we do with glaad. And I go back to the point I made at the beginning. It's not a recipe program. It is actually a minimal intervention.
Christian:
It's a framework to start with. It's not just about the knee control. It's about providing varying exercises to address impairments and tailoring and targeting to the individual. And if you do that well, you typically get reasonable outcomes. Not everyone benefits. So if I go to our GLAD registry data, we see three quarters of people would have a clinically meaningful change in their pain or quality of quality of life. So that means one in four don't have any benefit from doing the program. So our challenge going forward is to work out who those one in four are and how we can look at them a bit differently and maybe we can change it and looking at the whole population, how do we get them more physically active? Cause the other thing I can share with the listeners is that we only see a small, very modest effect on physical activity across the board when we use a program like glad. We need a lot more behavior change. And that's something we're working on in the background at the moment. So hopeful I'll be able to chat to you about that one day. Jared, in the future, looking
Jared:
Forward to it. I'm gonna, I'm gonna ask you Jen, before we finish off you, it's late for you Christian, and I don't know, is it what time is it over? It's noon. Noon-Ish. Noon time for an afternoon nap for you, Maris. Yeah. I'm gonna ask you both to, to prophecy something here and say, are we ever gonna find something that at scale has moderate to large effects hip and knee osteoarthritis or really any musculoskeletal pain whatsoever? Or are we always gonna run into this ceiling effect that people are so individual and pain is so complex and individual that everyone's always gonna respond differently to every single intervention? You know, so I'm not saying we shouldn't continue with clinical trials, absolutely do think we should, but are we gonna find this magic intervention that's gonna scale and, and help everyone to a moderate or large degree?
Marius:
I really hope so, but I have to, to be pessimistic and say, well, probably not in my lifetime, which is hopefully long,
Jared:
Not a hundred years to go. But,
Marius:
But I also have to say that and I always tease medical doctors about as, when, when, when people, when doctors refer to physiotherapy, it's because they don't know what to do. I mean, if they had the pill, they would give it, but they don't. And, and I mean, we as physios it's, it's unfortunate that, that we are left with all those difficult cases. I mean, look at low back pain, knee osteoarthritis, hip upper osteoarthritis, shoulder pain of various reasons. Nobody knows what's going on and they just send it off to us and then they criticize us for not working scientifically and yada, yada, yada. I mean, so, so we have the, the tough ones. So I hope that someday some smart doctor will, will find that secure and, and put be very rich and then we, we can focus on on some other patients. Yeah.
Christian:
My, my short answer, Jared, for everybody, absolutely not. We won't find it cuz it's too complex and belief systems are too complex and society and cultures is too complex and there's always gonna be people who don't respond to different interventions, but quality education and a quality tailored targeted exercise program is always a pretty good starting point. And that could be done in various different ways. Glad being one option, but there's many other options as well. And I think that's an important message for listeners. There's lots of, lots of varying options we have available. So if one exercise program doesn't work, doesn't mean that another one may not. So just keep, keep exploring the toolbox and don't escalate your care too quickly into potential things that are harmful. And I think Mari's point earlier, first, do no harm is a really key one.
Marius:
And I think that, that we also need to, I mean, it's, it's probably a more profound cultural thing that people are not really ready to accept, to live in with pain of, of any kind. So, so I think we should educate people. The, the population that pain in your body muscular system is part of life. You're not gonna go through your life without having pain for periods of life. And, and unfortunately, osteoarthritis is for the latter part of your life. And it we become older or older, so probably you'll, but it's not dangerous. It's not gonna kill you. You just have to be it, it and manage it just as good as you can.
Jared:
Christian, any, any, any last words?
Christian:
No, that's a, that's a, that's a great message to finish on is we do need to accept pain is part of life. That's how we conceptualize it and what we let it stop us doing and make sure we continue to be active and look after ourselves. Pain
Jared:
Is life. That's gonna be the, the headline of today's podcast. All right. It's profound. Life
Marius:
Is philosophical,
Jared:
life is paint, whichever way you wanna go, . All right, gen, thanks so much. You're both showing courage and bravery coming on here and, and having it chat and declaring all your biases, and I really respect you both. So thank you so much and I'm sure everyone will get something out of it. Cheers, fellas.
Marius:
Well, thank you for having us and thank you for the, for the discussion. Christian.
Christian:
Thanks. Thanks Jared, and thank you for answering my many questions.
Speaker 4:
Maris,
Jared:
Thank you for listening to this episode of The Shoulder Physio podcast with Christian Barton and Marius Henriksen . If you want more information about today's episode, check out our show [email protected]. If you like what you heard today, don't forget to follow and subscribe on your podcast player of choice and leave a rating or review. It really helps the show reach more people. Thanks for listening. I'll chat to you soon. The Shoulder Physio podcast would like to acknowledge that this episode was recorded from the lands of the Taraba Lang people. I also acknowledge the traditional custodians of the lands on which each of you are living, learning, and working from every day. I pay my respects to elders past, present, and emerging, and celebrate the diversity of Aboriginal and Torres Strait Islander peoples and their ongoing cultures and connections to the lands and waters of Australia.
