Hi, welcome back. This is James Fricton and the third part of the module on transformative care. And this is entitled, What interventions work for chronic pain? There are so many different interventions that have been developed over the years. All of them, to some extent, have some efficacy. But it's important to review what they are and to provide some criteria for which ones to choose. So, what we use typically in our clinic to determine what interventions work the best is the strategy of systematic reviews and evidence-based care. So systematic reviews really include all the randomized con, controlled trials. And I've discussed this in the, in a past module, that really show whether an intervention works or doesn't work. And how, and what are the adverse events? And on what patients it works with. Now, systematic reviews typically are based on other evidenced ra, randomized controlled trials, cohort studies, and critically appraised individual articles. So there's a variety of evidence that, that is out there. But this is the highest level of evidence to support. And so what I'm going to do is go through a number of systematic reviews for different treatments. Some of the reviews we've done, and some of it that, that are in the literature. So the methods we use for systematic reviews is that there's an extensive search of all the randomized controlled trials. In this particular case that was on PubMed, we also did a manual search for different articles that were not particularly on MEDLINE or PubMed but were still in the literature. And then you identify either meta-analysis or systematic reviews of RCTs, or treatment with at least one RCT. We evaluated the quality of the methods that were used in each of the RCTs or randomized controlled trials. And we compare the outcomes, both qualitatively, as well as quantitatively. And when possible, we wanted to conduct a meta-analysis with a Forest Plot that gives us an idea of what happens when we bring the data together. What is the aggregate results? So let me go through a few of these. Now there's many possible treatments for Mona Lisa. There are physical medicine and exercises, there's therapeutic injections and acupuncture, behavioral and psychological therapies. Pharmacological therapies, splits and orthotics, as well as surgeries of the joint. So, for musculoskeletal problems, this includes most of the different treatments that are out there. But first we need to understand the placebo effect. Because all of these are compared, to some extent, against a control group, and a placebo effect is the most commonly used control group. Now a placebo is the non-specific effect of a treatment due to a belief that it'll help. Obviously, we need to maximize this effect as much as possible. And placebos, interestingly enough, work about 30 to 40% of the efficacy of any treatment. While the active therapeutic effect of a treatment works only about 10 to 20% above placebo. That's where the significance lies. So, we need to make sure that we maximize the placebo since that is where most of the outcome and improvement is going to come from. Now, placebos have shown to be, to improve chronic pain but also many other conditions, depression, anxiety, et cetera. And, it's basically about mind over matter. And, we talked about neuroplasticity in the previous modules. Well, this is what happens. Basically, it, it, the mind-over-matter really impacts an active process, the brain. And it actually in, influences both the cognitive aspects, the immune system, the hormonal release, brain neurotransmitters, and others. So, the placebo effect is something we need to maximize, maybe not to this extent. A new report claims 50% of doctors have prescribed placebos, please take two Skittles and call me in the morning, says the doctor. So we, we still want to use treatments that have an active therapeutic effect above and beyond placebo. And in some cases, we may need to use multiple treatments. So let's review some of the Forest plots or meta-analysis that were done on, on a variety of different studies that, that we compared in our, our, at the University of Minnesota. Now, we did compare exercise versus placebo. And we had four studies that really used that were, were randomized controlled trials that used exercise against placebo. And let me kind of explain a little bit about the Forest plot. Now, each, you can see the squares here. That demonstrates whether or not that particular clinical trial favored exercise or did it favor a placebo? And then the, the triangle, the hexagon here, the parallelogram, the diamond shape, is the summary of the results from each of those four different clinical trials. And when it falls right down the middle here, that means there is no difference between the two. If it falls to the left, that means it favors the placebo. If it falls to the right, that means it favors exercise. And you can see where this diamond shape here is sitting. And the conclusion for this Forest plot is essentially with these four different clinical trials, that exercise shows a greater improvement than placebo in treating myofacial pain. And that was a significant effect. So, let's go through anoth, number of other Forest plots. What about transcutaneous electrical nerve stimulation? This was a combined, combination of three different RCTs with 146 patients. And you can see that the diamond was to the right and favored the treatment. TENS showed greater improvement than placebo in treating myofascial pain. And can be considered an effective but passive treatment. What about soft-laser versus placebo? This is usually directed towards an acupuncture point to change and stimulate the immune system, and relax the muscles. So you can see that there are five studies looking at soft-laser as a physical modality. And each of those did favor the exercise, or the treatment intervention, over the placebo. And the diamond was off to the right. So the conclusion here is soft-laser shows greater improvement than placebo in treating pain. And it can be recommended, again, as a passive therapy. So what about pharmacological agents? Now, in some cases we can't combine some of the agents with regard to a meta-analysis in a Forest plot. So what we do is try to summarize the efficacy, looking at the strength of evidence. If it's three plus, there's at least four positive RCTs. If it's two, to er, two pluses, it's two to four positive RCTs, showing more therapeutic efficacy compared to a control group. If it's one plus, it's one positive RCT. If it's a plus minus, it's conflicting evidence. And if it's minus, it means that there is negative RCTs, in other words, showed that the placebo is better than the intervention. So you can see that both NSAIDs or anti-inflammatory medications and acetaminophen had a number of RCTs and showed a three plus efficacy. The tricyclic antidepressants also showed significant improvement and had three pluses. So there is consistent evidence for both of these. But for pain, the SSRI antidepressants really had a mixed result. Whereas muscle relaxants and benzodiazepines also only had single RCTs for myofacial pain. Let's go onto therapeutic injections and acupuncture. And here you can see for trigger point injections, there was a couple of negative RCTs, but at least two to four positive RCTs. One study showed that a trigger point injection was equal to placebo while three studies showed more benefit. The Botox, interestingly enough, had a consistent effect with trigger point injections. There was eight RCTs, six placebo controlled studies, and there's three studies that showed them equal to saline. And three studies show more benefit for myofacial pain. Acupuncture and dry needling also have a very similar mixed effect. There are several studies that showed efficacy, but there's at least two studies that were, showed equal to placebo. So these treatments do have some documented efficacy, but with some patients it improves, some patients it doesn't. Let's look at Botox in terms of a Forest plot or meta-analysis. In this study, the, we looked at a huh, 484 patients from six different RCTs. And you can see, right here is the midline. And most of the RCTs were positive, showed significant. But there's three of them that are really right on the midline. So even though there wasn't a significant effect of Botox versus placebo, there was a slight overall trend showing that Botox intervention is better than placebo. But it's, really not significant. So let's look at splints. Now dental splints is something often used for TMJ and, and head and neck pain problems. And here is a Forest plot from meta-analys, including a meta-analysis of 344 patients. And in this case, you can look at the results from the six RCTs. Some of them were negative, some of them were positive. When you add those all together, there was a slight benefit showing placebo works better than plac than, or it's, that splint works better than placebo. And the result show a significant effect there. Now they are particularly useful for more severe head and neck jaw pain patients, as well as just used at night while they're sleeping. Now the next one is dry needling and acupuncture. You can see four RCTs were done. And you can see the results here, that most of 'em, two of 'em were pretty much right, equal between placebo and acupuncture. And two of them were successful and showed a positive effect. And you can see that the diamond did show an overall tread towards favorable effects of acupuncture compared to placebo. And that was significant. What about psychological and behavioral treatments? There's a meta-analysis of 24 RCTs that included focusing on relaxation strategy, cognitive behavioral treatment, and biofeedback. And you can see the number of RCTs here. And you can see that the efficacy was very significant, with multiple positive RCTs for each of these interventions. And it, perhaps, showed some of the most significant change in all of these meta-analyses that we've seen. So we can pretty much conclude that cognitive, behavioral and psychological treatment, cognitive behavioral treatment, works quite well. And here is a Forest plot, looking at cognitive-behavioral treatment versus placebo. And all of these five RCTs demonstrated a positive effect, and you can see where the diamond is here, off to the right. And there, it is a significant effect that CBT is better than placebo. And that includes muscle habit reversal, relaxation, biofeedback should all be considered for patients. Particularly those with day and night habits, anxiety, stress, feeling tension as contributing factors. So what about pharmacological treatments? The, our meta-analysis included 44 randomized controlled trials. And we looked at a variety of medications and I've talked some about some of those already. But here one that had more negative results. So triptans did not have any evidence of success for tension-type headaches. Glucasamine and chondroiton sulfate had one RCT that was positive for back pain. Some more recent research has come out showing that it really has a very neutral effect that's equal to placebo. Corticosteroids had no RCTs. And opioids had two RCTs, that was a, a positive finding as you'd expect. Now here's an RCT of NSAIDs versus acetaminophen. So what works better, ibuprofen or Tylenol? In this case, we had four RCTs we were able to combine together because they had consistent methods. And we found that the diamond showed that the NSAIDs favored acetaminophen. So we recommend an non-steroidal anti-inflammatories like such as ibuprofen or ketoprofen over acetaminophen. Now what about tricyclics versus placebo? In this case, we were able to combine five RCTs, and all the data for 484 subjects. And you can see that where the number one is here and most of these studies are positive. And so there is an overall trend showing favorable effects of tricyclics compared to placebo. But as you know, with any medication there are side effects. One is rebound pain. That means that by taking the medication it changes the neurochemistry adequately or enough to really have have it perpetuate the pain condition. So as this cartoon illustrates, I feel a lot better since I ran out of those pills you gave me. So, sometimes taking patients off medications takes priority or putting over, adding medications to their already piling pharmacy. And medications are not a panacea either. They are a lot of problems and failures associated with medications. And this particular study showed that the medications often took too long, did not relieve all of the pain, did not always work, pain often returned at the end of the medication, and it came with a lot of side effects. So the take home for this particular part of the module is that really, most treatment works. They, they, all treatments to some extent have some efficacy, but, their efficacy is only a little better, than placebo. So that 10 to 20% we do need to maximize, but we also need to maximize the placebo effect. And there are a varying degree of adverse events associated with any of these treatments. But, so we need to start out with treatments with less risk first and progress up to higher risk. And we'll discuss for the next part, both opioides and then follow that with talking about surgery. Thank you [SOUND].
