So in summary, this is Mrs Jones. She's our 32 year old patient with chronic migraines. She's been on Zomig for abortive therapy for several years which has worked pretty well for her in the past. But recently her migraines have been increasing in frequency and, today she's wondering if perhaps she should go on a prophylactic therapy. And specifically mentioned Topamax as that's something that's been recommended to her. How interesting, so she actually said Topamax. >> Mhm >> I wonder if maybe I had mentioned this to her a couple of months ago. Was there a reason she talked about Topamax? >> I think you had mentioned to her maybe about adding a therapy, and she has a friend that has taken Topamax before so she's heard about it. >> Oftentimes there's stuff out there that's in the press, they learn about it from their friends, and so. It's not unusual for patient to just come in and say, this is what I think I should be on. So maybe, let's back up a little bit. So she says she feels ready to start on a prophylactic agent at this point. Is that right? >> Yeah, it seems like they're starting to become frequent enough and really bother her enough that she feel like there's something else that needs to be done. >> Yeah, you had mentioned that now she's almost Using Zolmade almost weekly or a couple of times a week. And that really does kind of cross the threshold for when we would start considering a prophylactic agent. Did she mention any other things that she's doing to try and reduce the frequency >> Like any kind of deep breathing? Yoga? Changes in exercise or anything? >> Yes, she does do some of those. And she avoids chocolate. It sounds like she's done that for a long period of time. They don't correlate with her meds used or anything like that. >> Okay. >> It sounds like it's >> She's kind of been in status quo and suddenly they're just increasing. >> Okay, great question about the menses because that may change what we think about doing. So, Topamax, so it seems like we're at the point where we really should consider a prophylactic agent, which I think sounds reasonable. I would ask you to think about >> Is Topamax the one that you would use? So what do you know about it? >> I know it's an option, and there could be some other options out there, I don't know necessarily which one might be better in this case over things like beta blockers or other things like that. >> Good! So beta blockers would be another option that we could use. Are you aware of other classes or agents that we can use to reduce, reduce what she's going through right now. >> The only other one that comes to mind is the tricyclics. >> Okay, good, yeah, so tricyclic antidepressants. Boy that's an old class of agents and same with the beta blockers. But these have often been used, tried and true and Topamax is a newer agent. So, should we just use Topamax then at this point? Why consider those other agents? >> I think it'd be worth looking into what makes no sense for her given her age and, what her symptoms are and what she's already taking in terms of [INAUDIBLE] treatment. >> Okay, good. So we probably should look at this and try to get a sense. So This kind of gets into the category of comparative efficacy, trying to figure out is there one agent that's got better efficacy at a particular problem then another especially when you have these choices. So you're absolutely right, we do have these choices here. I think the best way to go about this might be to, let's start and just ask ourselves, do we know whether one is better than the other? So do you? >> I don't. >> Okay, good. That's good to be honest about what we do and don't know honesty, I haven't looked into this really in a systematic way in a while. So this is a great opportunity. In order to do that, I think we have to figure out the question correctly first. >> Mm-hm. >> That will help us structure this. So what are the good elements of a question that we would look at in terms of the resources to figure out whether one is better than the other? >> Mm-hm. So clearly define the patient that you're talking about, the population. >> All right. So what kind of patients would we be looking for in this study that we polled? Pre menopausal female patients. >> Okay so you would be specifically interested in how women do in certain agents as opposed to women and men. And that's a reasonable thought although I'll be honest with you sometimes it will be hard to find studies that will focus on one gender exclusively. So we may need to compromise there. But what kind of disease category are we looking at right now? >> Chronically Migraines. >> So chronic migraines as opposed to acute migrainous attacks or people that have had it for a brief, limited period of time. So that's great that you're classifying that, good. And then the intervention, let's just pick one. What kind of therapy are we interested in? That we should put in kind of the intervention part of the question. >> Mm-hm, so abortive agents or prophylactic agents. >> Okay. >> So we could pick of them, so Topamax. >> Mm-hm. >> Or one of the other ones, beta blockers. >> Good. So it's probably reasonable to pick Topamax, just given the fact that she's walking in with that expectation. You always want to pay attention to that, so that's a reasonable intervention. Then we always want to compare it with something. What would you compare as it relates to other prophylactic agents? You want to pick one or? >> Yeah, I think we could pick >> beta blockers or the tricyclic [INAUDIBLE], either one. >> Okay. No reason for us to get very specific about one versus the other. We can see what the literature comes up with when we look at it. But that's a good comparison group, as opposed to placebo. We know most of these things are probably better than placebos, otherwise they wouldn't have gotten to this point. So why waste our time looking for Placebo control trials. So then the most important part of the question really is the outcome. So what do you think about that? >> So I think, in this case it would be decreasing the frequency of which she's dealing with the migraines in a sense of inhibiting her quality of life. So is she able to decrease the duration and the attacks for migraines using this therapy. To prevent them from coming in the first place. >> Okay so you said two things in there, but frequency seems to be the first thing that you're looking at. But also the duration of the attack as well. Did you get a sense form her that the duration is lasting longer? Like the abortive agents just aren't working as well as they did before? Or is it mainly just that she's having too many of these right now. >> I think it's just that she's having too many. So probably focusing on the frequency. >> So good, let's just look at frequency. We might find studies that look at other things and then we'd have to weigh if it's good at reducing intensity, but not frequency. Is that a good agent? So I'm just postulating that that might be out there, that we would need to need to look at. So that's good, that's a good structured clinical question that we could look at the literature. So now the million dollar question, where are you going to go? Where should we go for a question like this? >> Yeah, I mean the clinical scholar's always an easy accessible site. >> The Google. >> But we're told not to go there. >> You're told not to go there >> Who tells you not to go there? >> Well most of the attendings in. >> Really? Sort of like look down upon it. So if you quote Google on attending rounds they'll kind of look down upon you. Okay. >> What's your thought on that? >> Well I'm asking you. So I mean Google's column was actually really good. It's important to know that Google as a search engine brings relevance, as its highest yield. So if you use a very simple search strategy, what's on the first page is just that's which is highest yield and most cited. So if you do Google scholar or Google, what you're going to see on the first page, which, let's be honest, how many of us click to page two, three, four, and five, what you're seeing on the first page is just almost the oldest articles because they have been cited the most and connected the most with others. So you actually have to use a little change in the fields to say sort by date as opposed to sort by relevance or connectedness. >> Okay, that's wonderful. >> But Google Scholar better than Google. Because Google Scholar is really limiting you to the peer reviewed literature to thesis presentations to annual meeting and conference presentations. So it's stuff that's kind of out there in the scientific community as opposed to a broad Google Search which honestly I wouldn't recommend for these kind of narrow focused questions. >> Mm-hm. >> Some people say Wikipedia. I'm impressed that you didn't, but why not go to Wikipedia. Let's just get it out there. >> I find that it's hard to often trust it because Wikipedia is an open source. Many people can edit it. There's not really great mechanisms to know how good the data is on there. >> I think it's reasonable to have that opinion, I share that opinion. It's really about the trustworthiness of it. People will say that it's crowd sourced, and so there's a trustworthiness built into that. But for newer pieces and newer topics, it's still pretty early in the crowd sourcing movement for that particular topic, so I just tend to stay away from Wikipedia because we have good alternative sources. Now the problem that people say is these alternative sources are also just cumbersome and clunky to use. So let's say we're not going to go to Google scholar. What would we do then? >> So I know there's a lot of different search engines that we have access to, things like. Ovid and Medline and PubMed. >> Yeah, right, right. >> And all those kind of things. I think it depends on which kind of literature you're looking for in terms of primary versus secondary literature. >> Good, so I'm glad you said primary and secondary. And I would say in this case, we should do secondary literature. And let me just tell you a little bit about why I would say that. So secondary literature really looks at, the primary literature is the research that everyone does and that's out there, but when you deal with a topic that's this common, that has been out there this long, you can pull an individual randomized control trial look at the data and then say, okay. This is helpful, but is there other stuff out there that we should be weighing? Is this the only study that shows the benefit in this particular direction? And you would have no way of knowing unless you looked at multiple primary sources. So you first look at a secondary source to see are these topics well studied and that there's this secondary literature, which actually pools the primary data presents best practices, best evidence and some expert opinion if you will. Now, those expert opinion have to be well reputed. So, I guess, I would say, secondary sources are good, that would probably where I go first. Systematic Reviews or practice guidelines. In this case, since we're looking at comparative efficacy, systematic reviews would be the best place to go. So, I would agree with you. I would say let's go to PubMed first. Because there's a way to search secondary and primary literature together. So, should we do it? >> Sure. >> We've got this here. I could also use the phone. But I think it's an easier interface on the laptop here. So let's get on this here. This is PubMed. PubMed is available across the world, it's a free resource, it's put through by the National Library of Medicine. - >> Okay. >> It's governed that way, and it's an open resource for anybody who's got internet access. In PubMed, there's a feature called clinical queries that I want to remind you of. Do you know what that is? >> I've heard of it, but I am not familiar with it. >> OK. You're not alone. There are a ton of people who have heard of it, but just don't know how easy a tool it is. It requires a single click. So you get there and you're on your primary search engine. But you just click on clinical queries here, and it takes you to a separate window. This separate window allows you to study primary literature and secondary literature at the exact same time. >> Great. >> So you don't have to kind of go to one place or the other. It's looking at the data and you'll be able to see them both simultaneously. >> Okay. >> So now you've got to define what you're going to search on. So what would you do? What would you say is the search terms? And I'll type them in for you, how about that? >> Migraine prophylaxis. >> Migraine. Whoops, sorry. Click on the window here. That would help. Migraine. Now you notice as I'm starting to type it, there's actually a bunch of specifics here. I use those because that means those are the types of searches that are highest yield in PubMed, so you're already having people do the work for you. So I see migraine prophylaxis right there, so I click on it. Now, should we click on anything else? Besides migraine prophylaxis? >> Topomax since we discussed that specifically. >> Look at that. I types Topomax, but then Topyramid came up. Is that the same thing? >> The generic name. >> yeah, it is the generic name. Good. So here we go. So now we're going to search on it. And look what happened. In the primary study we got a bunch of randomized control trials. And in the secondary we've got a bunch of systematic reviews. So we actually can then look through and find a couple that might be relevant. Now remember you want comparison groups and that sort of thing. So we might need to look through here, look on the first page. Do you see anything here on the first page that might be helpful? Well if we saw all of them since we looked at, we're looking at secondary literature, let's kind of go down and see there any here that look good? >> There was a, yeah. >> What is that? Topiramate for the prophylaxis of episodic migraine in adults. And it's a Cochran database. >> Mm. >> The systematic reviews. Cochran's a pretty good resource. >> Yeah. >> So again, you're trying to get other people to do the work for you so that you can look at the data. You have to be able to analyze the data and be able to interpret what it says but you know that Cochrane is pretty high quality and they do a bunch of systematic reviews all the time. It's a volunteer organization and it's international, so this could be a trust worth resource. And it says Topiramate for the prophylaxis of episodic migraine in adults. That sounds pretty good. >> Sounds pretty ephitical. >> Is there other's that are out there that you might want to think about? >> Preventative pharmacological treatments. For episodic migraine in adults. >> Okay, so that's a good one too. Remember the difference between this one, the Cochran only focuses on topiramate and this one, from J. Jim in 2013 might focus on all the different agents. And remember we're thinking about multiple agents. >> Mm-hm. So this one could help answer the patient's question, this might help answer our question and use [INAUDIBLE] as one of those. It's a pretty recent one, so it's probably going to include Topamax in there as well. So immediately, you've got a couple of systematic reviews that we could dive into. >> Sounds great. >> So you feel comfortable with this rather than going and looking at an individual randomized control trial? >> Yeah, I think so. >> Why? Why is it okay to just stay here and not look at the primary literature? Why do you feel [INAUDIBLE]? >> So I think as you said you'd have to go through many randomized control trials to kind of get an assessment of the overall body of evidence that's out there and this does that for you. I think if you had a question about maybe a specific article and a review, let's talk about one of these. You could go look at that then and try to make your own assessment. >> That is great. So really, one of the advantages of using sort of an internet or a web based application is that you could look for primary studies within the secondary literature and then click on those and then see the primary studies as well. That's a neat technique that people can use especially when you have more time to dive in depth but at this point, these two seem like pretty decent studies to look at. All right, so let's go print them out. And then we'll look at them. >> Sounds good.
