Alfred001

But that's all we want to look at in this situation. Cancer. Not sure what you mean by this, but the experiment is set up to see whether people who take metro have more cancers than the people who don't, I don't see why that would be impossible to determine, provided an adequately large sample to factor out chance. I could have sworn that this is how it was explained in a number of youtube videos I watched on the topic! Ok, I definitely had a misconception about what a CI is. Nevertheless, that study still doesn't allow us to say whether there's an effect or not, right? The upper bounds of the CIs are 6+ and 2+, which means the effect could be of that magnitude.

Ok, can you explain what you meant by that part? Doesn't the CI mean that the actual effect is somewhere in that range? If so, why is it then not more likely, since so much of the range is above 1 that there is an effect? In fact, the CI for the 12< year follow up group is 0.92-2.20 - almost entirely 1<. Can't we say there that an effect existing is significantly more likely than not existing, although it not existing (or a protective effect existing) is a possibility as well? Right, in other words, we cannot know from the study whether there's an effect. Why wouldn't it be if the effect is strong enough or the sample large enough? I mean the CI for the 12 year group is fairly narrow and almost entirely above 1. If you added some more pairs and narrowed the CI further maybe you'd get entirely above 1 and be sure that there's an effect. And to begin with, the CI could have been 2-3, if this were some other drug with a stronger effect.

So it's actual incidence of cancer, divided by person years in the study and then multiplied by 100 000? I'm not sure what you mean by normalization. Why not just explain what you mean instead of getting petty? Ok, but the most we can say from this study, based on that CI, is that we don't know whether there is a greater risk in metro users, not that there isn't one, and in fact, given that the great majority of the interval lies above 1, it seems much more likely that there is one than that there isn't one, no?

Yes, I understood that part. It's still the people getting the cancers. Doesn't change what's strange about it. I understood that as well, I'm not sure what you're getting at with this part. Yes, but that's what I'm asking, how is it possible to have as large a sample as they did and find as large an effect as they did and for it to be down to chance? 608 pairs in 15+ years and over twice as many cancers in the metro group, how could that be chance? Even if we accept their confidence interval, the value is 0.82-6.12. Most of the range of the interval covers a greater incidence of cancer by a factor of up to 6. At best, based on this, we can say it's unclear whether there is an effect and that the effect could be large (granted, also could be no effect), but we can't say there is no effect. Does anyone know how they would have calculated that CI and that p value? I mean in concrete terms, with these specific numbers. Point taken. When I said two papers, I was referring to what the Japanese study provided as references for their claim. However, the first study is talking about all ABs and different classes of ABs in aggregate. I would be interested in the safety data on the individual antibiotics that are used in H pylori therapy and therefore represent alternatives to metro for that indication. Those are clarithromycin, tetracycline, bismuth (I guess in some sense not an AB, but has the effect and used for the purpose), amoxicillin, levofloxacin and a few less commonly used ones such as moxifloxacin and doxycycline. The FDA issued a fairly stern warning for quinolones (levofloxacin, moxifloxacin...) in 2016. for some severe side effects, including potentially permanent ones, but I don't know how common those are. I don't know much about the safety profile of the other drugs, outside of penicillin allergy in connection with amoxicillin.

I will respond to this as soon as I have the time to read the studies, but in the meantime, does anyone have the answer to these questions? I really want to understand that study.

The claim about other ABs causing cancer is based on two studies alone. The nurse study and the clarithromycin study. The CLA study looked at all cause mortality, not cancer and median followup was 3 years, so you're not gonna detect any cancers with that. The epidemiological studies they reference lack data on dose and duration, so I don't know what the basis is for the claim about the safety of a short course of metro. EDIT: This is in response to Charon's post form the previous page.

This paper critiques some of the studies used to arrive at the "no significant effect" conclusion in the earlier review: https://onlinelibrary.wiley.com/doi/abs/10.1111/hel.12575

Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis This paper provides an excellent review of the evidence. EDIT: Ok, they say later on in the paper that they think there is good evidence that it doesn't have a significant carcinogenic effect in man. Which isn't not to say there isn't one:

That's almost exactly what I said in the VERY POST you were responding to. At this point I'm beginning to think you're trolling me. There's no way anyone can be this... I can't say what else I might get another warning. Like literally in the paragraph you're correcting me on I said virtually the exact same thing as your correction. And we would know about it, how? Again IN THE VERY POST YOU WERE RESPONDING TO I quoted what the paper said. Is there some way to make the font bigger? I'm afraid in the next post John will tell me, YEAH, BUT IF THE EFFECT WAS BIG WE WOULD KNOW ABOUT IT. Anyone wanna bet that's gonna be his next post? Yeah, if the effect was 100% we would know about it, great argument! Anyway, I'm done engaging with you. If anyone has an intelligent point to make on the topic or can bring actual evidence to the table like TheVat, I'm happy to continue this discussion. Hmm... why am I getting warned and not the guy who started the incivility? (literally his only contribution to the thread) Anyway, doesn't matter... Great find! This is, for a stark break from the norm, a valuable contribution to the thread. However, can someone explain what I'm not getting in this part: 1,336 and 564 cancers among users and non-users in at least 15 years of followup? Doesn't that mean there were 1900 cancers in 1219 people??? More cancers than people? I mean I know a person can get cancer multiple times, but THAT many multiple times? I doubt they counted recurrences as individual cancers and even if they did... Or am I completely misinterpreting things? Also, incidence of cancer in 15 years of CANCER-FREE followup... what? What am I not getting here? And then thirdly, 2.38x more cancer among metro users, how is that not significant? Ok, I see that the CI ranges from sub-1 to 6.12, but isn't that CI so wide as to be meaningless? And how likely is it that a 2.38x difference in 15 years is just down to chance??? Also, the limitations here are a bit worrisome, especially the absence of data on dose, duration and compliance.

Seriously guys, is there a single person on this forum who can reason well? This point has been made ad nauseum by Charon alone, let alone all the other people who've brought it up. Like AD NAUSEUM. Yes, it's a cost benefit analysis. To make that cost benefit analysis, we need this: Understand? In other to make the cost benefit analysis you need to know what the cost is and what the benefit is. We know what the benefit is, but we don't know what the cost is. So I've asked Charon for a reference for his claim about the benefit being greater than the cost at least twice on this page alone and notice how he's ducked it both times, because he doesn't have it and he was just making a claim with no evidence for it. (love it when people debate in good faith!) Also, you're reprimanding me for name calling? Who started the uncivli behavior here? Me or the guy who jumps in with snarky comments, never contributes anything to the debate and then behaves immaturely when asked to back his snarky remarks up.

If you're gonna talk shit then you should have the balls to debate and back it up, otherwise stfu punk. EDIT: Yeah, downvote my post, but UNDER NO CONDITIONS engage, pussy 😄 You know it wouldn't go well for you.

Explain.

You keep ducking. Your claim is the risk of not treating is greater than the risk of treating with metronidazole. Ok, provide a study that proves that. Show me a study that compared an untreated group with a metro-treated group and found less incidence of cancer in the metro treated group. If you don't have that study then you can't make the claim that your whole position is based on. Don't obfuscate and change the subject as you just did. Do you or do you not have such a study?

Which paper has shown reduction in cancer risk with metronidazole treatment relative to no treatment? And did it take into account gastric cancer only or all cancers? The reviews I posted showed increased incidence of cancer after metronidazole treatment. Again, source for this claim? Again, metro is not the only AB used in H pylori treatment, so relevance to cancer risk? Also, penicillin allergies are considered when selecting ABs for H pylori treatment, no other AB commonly used for H pylori treatment has allergy issues associated. Also, metronidazole generally has the highest rate of resistance, higher even than clarithromycin (although, granted, resistance can be overcome, but the point is moot to begin with).

Any response to this, @CharonY?

1. OMG, my point is that if you know the relative risk you're NECESSARILY gonna know the absolute risk. 2. How many times are you going to repeat this. It's not a difficult concept, I get it. Again I ask you, show me the study which shows cancer risk is higher in untreated H pylori relative to metro treatment. Why did you ignore that question? Again, metro is not the only AB used in H pylori treatment.

Jesus Christ, how do you not understand that it's the same thing? If you make a study and compare a group in which H pylori was not eradicated to a group in which it was eradicated with metro you're gonna know the absolute risk lmao. So where is the study that did that? Where is the study that established what % of people who take metro for H pylori end up with cancer vs what % of untreated patients get cancer? And this is all ignoring the fact that METRONIDAZOLE IS NOT THE ONLY ANTIBIOTIC IN THE WORLD. It's not metro or don't treat the infection. You can treat it with different antibiotics. I'm genuinely baffled as to why you're bringing up a single study when I quoted two reviews of the literature. Yes, not every study has found an effect. Many have. You can't arrive at a conclusion based on one study.

Yeah, the situation right now seems to be that there's evidence suggestive of a carcinogenic effect in humans (in vivo). Some studies find no effect, but others do find an effect. As the review article states, it's a controversial question and it seems to me that it's crazy and irresponsible to be so widely prescribing a drug which seems to have a carcinogenic effect of unknown potency. Right now metro is part of the regimen that most guidelines recommend as the first line treatment for H pylori and the tendency is to prescribe increasingly higher doses (because metro resistance is becoming increasingly prevalent and you need a higher does or duration to overcome it).

BRO, this symptom again? Ignoring things that were said 4-5 posts ago. Let me quote again: Just peruse the study at least, just for the love of god, don't ignore what was said within 10 posts ago. https://pubmed.ncbi.nlm.nih.gov/29595104/ We've been over this a MILLION times. We CANNOT know whether it provides a net benefit if we don't know what it's risk is. You cannot compare the risk of the disease to the risk of cancer from metro if you don't know what the risk of cancer from metro is. Like the review article said, there is inadequate evidence to establish whether metro increases risk of cancer and by how much. Really, I cannot repeat the same argument any more times. If the risk of driving without a seat belt is x and the risk of taking a mystery pill is unknown, you cannot know which is worse. But let's just table this point, can I ask you to please do that, just to make the discussion simpler? I ACKNOWLEDGE and RECOGNIZE that it is a matter of risk vs reward, ok, now, let's set that point aside and nevertheless discuss the matter of whether metronidazole in H pylori type course (2 weeks, 500-1500 mg per day) increases risk of cancer.

??? That's what we'd debated for two pages. You claiming no effect exists or is so small as to not matter, me saying that, as the paper says, there's inadequate evidence to know how big the effect is.

Had to drop this debate due to being busy, but reviving it... So, here's a review article making my point: https://pubmed.ncbi.nlm.nih.gov/12052431/ Another one https://pubmed.ncbi.nlm.nih.gov/29595104/

One of the things that most gets on my nerves in a debate is when a person can't keep track of arguments that were already made and already refuted, but this is even worse. Do you SERIOUSLY not remember that you made this argument FOUR POSTS AGO and I answered it THREE POSTS AGO. Like not on the previous page, THREE POSTS AGO.

Again, I've said like 10 times I've not done a systematic review of the literature. Do you know that it has been done? You did not understand what I wrote. I'm not sure I can make it simpler after so many posts, but let me try: We have evidence suggestive of carcinogenic potential. We need to test to know how large the risk is. We don't need to know exactly how large it is, knowing that it is smaller than 1 in 100 000 would probably be sufficient. Let me know which part of that you don't follow, I'll explain easier if I know where you're getting lost. Show me the meta analysis with adequate statistical power and followup. 😄 I can't... This is exactly what I explained to you in the previous post. Man, use your head. I feel like you're just arguing to be arguing, because there's no way you really believe arguments this bad. Cancer is a long gestating disease with a million risk factors. Think about it. If a person gets cancer, would they be able to link it to a course of metronidazole they took 10 years ago? Would they even remember taking it. Come on, man. Source? No single studies looking at one cancer with short followup and small sample size.

I don't understand what statistical power has to do with what I said. I said we need to do a systematic review of the literature to know what the totality of evidence says and not look at 4-5 studies. But don't you understand that you don't have to find it? If you have 100,000 subjects and you don't find an increase in cancer risk then you can say that, if an effect exists, it is smaller than 1 in 100,000 getting cancer. That is sufficient for us to know that the risk, if it exists at all, is miniscule and we can now know the drug is safe or at least safer than not treating H pylori. I don't understand why people keep bringing up things I've already addressed. It would not be expensive because it would not be a trial, but an observational study. OMG, of course it would change clinical practice. If we found out that the risk was higher than the cancer risk conferred by H pylori we would use a different antibiotic to treat the infection. That's the whole point. Again, I've already explained this at least twice. Again, it has been stated so many times already - we don't know what the cancer risk associated with metronidazole is. Literally the whole point of this thread. And, again, when I say we, I mean we here in the thread. Perhaps studies to answer the question have been done, we'd need to do a comprehensive review of the literature. Right now we have a bunch of studies with conflicting results.

From 1:40 on, you can hear him give an unflattering description of Feynman, describing him as obsessed with generating anecdotes about himself. Now, at the moment, I'm reading Surely You're Joking, Mr Feynman and I came to the book having already heard these criticisms from MGM and I was looking for sign of these kind of character traits and while I thought I saw them in some of the early chapters (where he would describe these counterintuitive systems that he would come up with for doing this or that that other people couldn't appreciate), later on there were things that ran contrary to this image of an egomaniac obsessed with making myths about himself that MGM describes or implies. For example he would often talk about how other scientists were superior to him at this or that or openly talk about how he was afraid of not living up to a masculine ideal in sports or physical confrontations... he doesn't seem in the book to have a problem with being honest about his own shortcomings or where others were his betters. I found him, in reading the book, a delightful character. Anyway, I was wondering, are there any other people who knew him who made similar criticisms of him? And do you think there really was in him this desire to build the myth of Richard Feynman?