S7 E8: Longevity of THR; GLP1a for Addiction; Analgesia for Kids

Welcome to the Hot Topics podcast from NB Medical with Dr Neal Tucker. Three new research papers to help us along our way in general practice this month.

First, how long do modern hip replacements last? How does this new data change our conversation with patients?

Second, it's thought GLP1 agonists could have a role in addiction management, but so far, research has failed to show a definitive benefit. Could new data from the US on veterans with type 2 diabetes show a different picture? 

Finally, what analgesia would you recommend for a child in pain? This new paper compared ibuprofen with or without paracetamol or hydromorphone - yes, an extremely potent long-acting opioid for kids. Good idea? We find out.

References

Lancet Hip replacement longevity

Lancet THR Editorial

BMJ GLP1ra and addiction

BJP editorial

JAMA Analgesia and Child  

www.nbmedical.com/podcast

Transcript

Introduction

Neal Tucker 0:00

It's Friday the 13th of March, and this is the Hot Topics Podcast. Welcome to the Hot Topics Podcast from NB Medical. With me, as usual, Neal Tucker, strap in for a wild 20-minute ride through what's new and interesting from the world research rubbing up against the chaos of general practice.

What will we be covering?

Neal Tucker 0:29

Three papers for us to look at today, as usual. We're going to unusually start off with some orthopedics and look at new data on how long hip replacements last. I think this is really relevant to our patients. Could influence how and when we consider referring them for operation. Second, we've got some new research making the role of GLP1 receptor agonists in addiction management just a little bit clearer. And then finally, what pain relief would you suggest a child takes if they are in pain?

NB Medical News

Neal Tucker 1:01

NB news first, we've just started our new hot topic spring 2026 course last week. So that's available on demand now if you want to see it straight away, or we'll be running it live again in April. That's April the 25th. In the meantime, we've got our fantastic women's health course tomorrow. That depends on when you're listening to it. It's the 14th of March. Do check that out. Absolutely brilliant course. And then we've got a little break for Easter and we start everything again afterwards. As ever, everything is available on demand on the nbmedical.com website.

Neal Tucker 1:36

For NB Plus users, we've got a new tool in your NB dashboard as well. So 'Ask Archie'. Yes, we've jumped on the AI bandwagon. We've developed an AI tool which can help you find what you need to find from our NB portfolio and help you manage your patients as best as you can. Crucially, it's not scouring the internet, it only uses material from the NB Medical website. So all of that has been written by humans, by us as GPs, so that you can be confident in the recommendations. It's got a free test period until the end of April, so do check that out.

How long do modern hip replacements last?

Neal Tucker 2:12

Okay, let's crack on with the research. And paper number one. This was published in the Lancet a couple of weeks ago. So have you ever been in the position of suggesting to a patient who has joint osteoarthritis, who is in pain, who is being limited in day-to-day activities, who has tried physio maybe, or perhaps joint injections, who's tried all of the analgesia and discovered, like so many of our patients, that when bone is grinding on bone, no amount of pain relief is actually going to work.

Neal Tucker 2:41

So have you been in the position of suggesting they try and tough it out for a bit longer because they're just too young for a joint replacement? If they have it done now, it will fail within their lifetime, and revision surgery remains complex, potentially dangerous, and even more prone to failure itself.

Neal Tucker 3:01

Delaying joint replacement when someone's got severe osteoarthritis, of course, has its own risks, not only directly impacting their quality of life because of pain, because of reduced mobility, but as people are able to do less, of course, they start to decondition their muscles atrophy, and when you eventually do get your operation, you may never recover your pre-joint damage physical ability. So it's a really important question. How long does the average joint replacement last? Well, this paper titled Survivorship of Modern Total Hip Replacement to 30 Years answers this exact question for hip replacement.

Neal Tucker 3:39

So existing data published in The Lancet in 2019 actually gives us the answer already. That figure is 58% at 25 years. So almost half of these will have failed by 25 years, which doesn't sound that great to me. I mean it's good in so far as 25 years is quite a long time. No one's buying a dishwasher these days, expecting it to last 25 years. So score one for the orthopods. But if you're in your 50s or your 60s, there's a good chance you're going to outlive your prosthesis and it's going to fail at exactly the point no one wants to do revision surgery on you, leaving you in a right pickle.

Neal Tucker 4:18

Now, there was one major flaw with this 2019 research, and that's that it included all hip replacements from the last few decades, including those which were using older techniques and technologies and that don't reflect modern practices. And that's what this new study aims to rectify. So the authors focused solely on modern bearing surfaces, highly crosslinked polyethylene, which hugely reduces wear and subsequent aseptic loosening compared with older acetabular implants. Oh man, as I even sort of hear that in my head, I realize we're sounding way too orthopod technical right now. But don't worry, we're not going to keep on going down this route. We're going to keep it in the real world. So this study is a systematic review and meta-analysis of published clinical studies and also data from eight different national registries, including the UK, Australia, Canada, and a range of European countries, which had a minimum reporting time of at least 10 years.

Neal Tucker 5:19

The primary outcome was survivorship of the hip replacement, defined as time from the operation to first all-cause revision. So they were pulling data on who needed a revision to look at the survivorship rates, and then they reported the findings at 10, 20, 25, and 30 years. The latter was largely an extrapolated estimate based on available data given that this newer polyethylene material was only reduced in 1998. So the year I started medical school, that feels like quite a long time ago. The results were unashamedly positive. So 1.9 million people were included, or 1.9 million hip replacements. I don't think the orthopods would class them as people, would they? They just look at the joint. And at 20 years, the survivorship estimate came out at 93%. That sounds to me pretty high. At 30 years, it was still 92%, so still really high. I think this is pretty remarkable. After 30 years, less than one in 10 people need to have revision surgery for their hip replacement. These things are remarkably durable. And they could obviously go longer as well. Could keep going at that rate. If I needed a hip replacement in my 60s, that means there's a good chance, even if I live to 100, it's still going to be going strong.

Neal Tucker 6:49

There's further good news. The editorial highlighted that the 10-year estimated failure rate was 4.4% in the study, which first tells us that if your hip replacement is going to fail, there's a good chance it's going to do so early on. And if you're fine by 10 years, there's a really good chance that it's going to outsurvive you. But they also point out that 4.4% is higher than failure reported in the UK National Registry, which is actually less than 2%. So you might have to wait three years for a hip replacement on the NHS, but it sounds like you're in pretty safe hands when you finally get one. Of course, it would be remiss of us not to point out the caveats of the papers. And the key one is that by using revision data as the marker of failure, it's of course not capturing some people that might have joints that are failing or at least giving them some gyp now, but don't have revision surgery. Maybe they're too old, maybe they've got comorbidities and no orthopod is going to want to touch them. Well, capturing this group, of course, would be much more difficult on scale, but would of course provide a clearer picture of the true rates of lasting clinical benefit.

Neal Tucker 8:00

Nevertheless, compared to the existing data we've had up till now, this study provides hugely reassuring data for patients considering hip replacement and could really change our conversations with patients. If we're confident that the majority of hip replacements are going to last 30 years, then whilst we might still need to consider, of course, the basics exercise, physio, weight loss, pain relief, steroid injections, and so forth, for those who have enduring pain and limitation at relatively younger ages, trying to delay surgery due to concerns about longevity is largely unnecessary.

Is there a role for GLP1 agonists in addiction management?

Neal Tucker 8:38

Now, when did we last talk about GLP1 receptor agonists on the podcast? It's got to be at least four weeks or so, so time to bring them back into the fold. And our second paper, this latest paper on them published in the BMJ this week, exploring their potential in addiction medicine.

Neal Tucker 8:59

This is an area which has been postulated GLP1 receptor agonists could have a significant role in, but as yet we don't have convincing data that they actually benefit. The authors set out the case in a separate BMJ opinion article. As they explained, GLP1 receptors are abundant in brain regions linked with reward, motivation, stress, and addiction. They have the ability, the medications, to cross the blood-brain barrier and act on these receptors so they could potentially dampen addiction pathways and not just be specific to one type of addiction like most medicines that we prescribe would be, but potentially could work across all different types.

Neal Tucker 9:46

So far, sounds so good in theory. But we've already talked on the podcast about a small trial looking at the effects of GLP1s on harmful alcohol use, and the benefits weren't that convincing. What does this paper add then? The best way to look at this would of course be a randomised controlled trial, but this has its own inherent problems. They take years to get the numbers needed to give a meaningful result can be difficult, time consuming, and potentially very expensive. And when you might already have a whole bunch of patients who have basically done the trial for you just in the real world, why not use this data instead? And that's what these US researchers, the authors of the paper, have done. It's an observational study, but it's an emulation study as well, set up like a randomised controlled trial, trying to emulate an RCT and provide slightly stronger data without the need for all the apparatus associated with a randomised controlled trial.

Neal Tucker 10:47

The title of the paper is 'Glucagon-like peptide 1 receptor agonists and the risk of substance use disorders among US veterans with type 2 diabetes, a cohort study'. So it still acknowledges this is a cohort study. They wanted to see if GLP1 agonist use was associated with reduced risk of alcohol or other drug use disorders in people with firstly, no history of substance use disorders, and secondly, those who have an existing condition and whether it could reduce use or risk in that group as well. As you might have guessed from the title, they were of course looking at US veterans, presumably a group with a high risk for substance misuse already. They also had type 2 diabetes, and therefore they may also have been issued a GLP1.

Neal Tucker 11:40

Now, about 60% of them were on semiglutide, about 20% were on Liraglutide, and about 15% on Dulaglutide. Only 1% were on Tirzepatide, presumably because it's a relatively newer drug and the period at which they were examining. The study then emulated eight parallel new user active comparator target trials using electronic health records. So basically they were setting up like little RCTs looking at one for alcohol, one for cocaine, one for heroin, etc., and then compared use of GLP1 receptor agonists against SGLT2 inhibitor use, which of course no one's expecting SGLT2 inhibitors to be good for addiction, even if it seems like they're being used for absolutely everything else. They're good for everything else these days, except maybe itchy groin disease and UTIs and DKA. Ugh, okay, I've gone got sidetracked down an SGLT2 inhibitor hole.

Neal Tucker 12:41

Anyway, the results showed that compared to SGLT2 inhibitors, GLP1 agonists were associated with a reduction in risk of disorders related to alcohol and drug use. Users were about 10 to 25% less likely to develop substance use disorder, with that reduction seen across the board, although at slightly different levels depending on which category you were looking at. The data also showed that if you already had a substance misuse disorder when you were initiating a GLP1, then that reduced a range of outcomes. So, for example, ED visits went down by 30%, drug overdose went down by 40%, and substance misuse disorder mortality, so death as a result of your substance misuse, went down by 50%.

Neal Tucker 13:33

I have to say, I came into this paper with substantial skepticism about GLP1 receptor agonists in addiction. And on the basis of the data that they've got here, actually, a result which halves mortality in people with existing drug dependency sounds pretty impressive. The figure for use as a preventative is, of course, much less compelling. But for those with existing disease, then perhaps this does suggest that there is a role. Of course, we need to remember who's being examined here. This is US veterans. Generally, they were older men, they've all got type 2 diabetes. We can't just simply extrapolate the findings to our 20-year-old patient who's got heroin addiction. We have to remember that this isn't a randomised controlled trial, no matter how much the authors try and make it look like one. We need to remember, as the editorial points out, that GLP1s haven't been tested against no treatment or evidence-based addiction pharmacotherapies, let alone non-drug treatments.

Neal Tucker 14:41

The editorial calls for randomised controlled trials now to fully explore this potential more definitively. They'll, of course, need to focus on safety as well. There's a tendency in these studies to really focus on the positives and leave lots of unanswered questions around safety, and that's really important with these medications. What are the effects in people with very heavy alcohol consumption, with mixed illicit drug use, who maybe don't eat regularly, who maybe are underweight already and prone to sarcopenia? What happens when you stop the medications? Patients who are using these drugs for weight loss describe the medication switches off that noise, that food noise that kind of chatters away in the back of the brain constantly. And that's great. When they stop it, it comes back. So are you then going to risk a relapse spike if you're using it for addiction?

Neal Tucker 15:40

This paper is full of really interesting data, but I think it's too early to change clinical practice here. I think there still remains lots of questions that need to be answered. And of course, we can't assume we can extrapolate the findings from this paper, from this study population, to all of our patients who have addiction. That time may come eventually, or indeed it may not. And of course, that's why we keep doing the research.

What analgesia would you recommend for a child in pain?

Neal Tucker 16:07

Okay, on to our final paper published in JAMA this week. This looks at the best pain relief for children who have hurt themselves. I think the reason this paper caught my eye is because sometimes some studies just seem totally bonkers to me.

Neal Tucker 16:27

There are potential learning points for us here in GP Land, but okay, let me set it out. Here's the bonkers. If you had a child who had a musculoskeletal injury, would you rather give them ibuprofen, ibuprofen with paracetamol, or ibuprofen with hydromorphone? Not used hydromorphone before? It's like oxycontin. Yes, we've all seen the TV shows about that, only it's more potent and more addictive. So the question is, is it a good option for kids? The mind boggles.

Neal Tucker 16:59

But in its defense, this Canadian study, yes, it's not American, it's Canadian, which makes me feel slightly better. It was looking at children with limb injuries that didn't require surgery, that presumably hurt a lot, and was looking at these options as acute treatment. I don't think there was any suggestion the kids are gonna get sent home with a month of the good stuff and a fast track to 'Smack Alley'. It does as well answer a serious question: how good is ibuprofen for pain relief in kids and how much better is that pain relief if you add additional analgesics? Nice bit of alliteration there.

Neal Tucker 17:38

This is a randomised controlled trial of almost 700 children put into three groups. So one ibuprofen given at 10 milligrams per kilogram, two ibuprofen plus paracetamol at 15 milligrams per kilogram, or three ibuprofen plus hydromorphone at 0.05 milligrams per kilogram. In case you're interested, hydromorphone is seven and a half times stronger than standard morphine, which for my 11-year-old son would mean he'd get about two milligrams, which is equivalent to 15 milligrams of standard oral morphine, which sounds like a pretty hefty dose for an opiate naive kid. But what about the pain?

Neal Tucker 18:21

So the study showed that there was no additional benefit to adding either analgesic to ibuprofen. Ibuprofen monotherapy was as good as either of the combination options. That's not to say that ibuprofen by itself is a magical treatment. The authors report that only just over 20% of children had their pain adequately relieved at 60 minutes with monotherapy. It would be great to say there's something to improve on that, but combinations, as they've been looked at in this study, don't. They don't improve things, so they can't be recommended. Plus, the opioid spiked the rate of adverse events from 6% in the ibuprofen, plus or minus paracetamol groups, and that was 6% who had only mild side effects, up to 28%, of which one in five were moderate. Whatever that actually means, they don't really explain it in the main body of the paper. Presumably you're getting like eight-year-olds going around seeing pink elephants flying around the room before puking everywhere and then not having a poo for five days.

Neal Tucker 19:30

Phew. Looks like we're off the hook with the hydromorphone people. What about just giving paracetamol instead of ibuprofen? Many of us might think that that's an even safer option. Well, it is an option, but as the paper explains, at least in the context of musculoskeletal pain, existing research suggests that ibuprofen edges out paracetamol whilst having still a very good safety profile. And at least in international guidelines, is recommended first line alongside non-pharmacological methods. 23 years ago, when I was an orthopaedic house officer, we were avoiding NSAIDs after fracture because it was felt it might delay healing of the bones, resulting more non-union. But at least in kids, this paper points out that that's turned out not to be an issue. So dispelling something that I've held in my mind for at least two decades now. I've got no idea about adults, I'll stick that on my PUNs and DENs list.

Neal Tucker 20:31

Anyway, in conclusion, all things being equal, if a kid's arm or leg hurts, give them some ibuprofen and skip the rest.

Neal Tucker 20:40

That wraps it up for this podcast. Thanks for tuning in as ever. We'll be back after Easter. I hope maybe you get a little bit of a break. We'll have more research reviews for you next time. Until then, don't forget to check out the nbmedical.com website for all the good stuff coming up. Remember, you can always get in touch as well on hot topics @ nbmedical.com and various social media outlets.

Neal Tucker 21:05

And in the meantime, look after yourselves. You're worth it. Bye-bye.